Noemí Marín Atucha - Academia.edu (original) (raw)
Papers by Noemí Marín Atucha
Clinical Case Reports, Jan 19, 2021
Our results do not support any effect of FVIII on platelet function in patients with severe HA tr... more Our results do not support any effect of FVIII on platelet function in patients with severe HA treated under the regime of prophylaxis.
British Journal of Pharmacology, Jan 13, 2014
The negative affective states of withdrawal involve the recruitment of brain and peripheral stres... more The negative affective states of withdrawal involve the recruitment of brain and peripheral stress circuitry [noradrenergic activity, induction of the hypothalamic-pituitary-adrenocortical (HPA) axis and activation of heat shock proteins (Hsps)]. Corticotropin-releasing factor (CRF) pathways are important mediators in the negative symptoms of opioid withdrawal. We performed a series of experiments to characterize the role of the CRF1 receptor in the response of stress systems to morphine withdrawal and its effect in the heart using genetically engineered mice lacking functional CRF1 receptors. EXPERIMENTAL APPROACH Wild-type and CRF1 receptor-knockout mice were treated with increasing doses of morphine. Precipitated withdrawal was induced by naloxone. Plasma adrenocorticotropic hormone (ACTH) and corticosterone levels, the expression of myocardial Hsp27, Hsp27 phosphorylated at Ser 82 , membrane (MB)-COMT, soluble (S)-COMT protein and NA turnover were evaluated by RIA, immunoblotting and HPLC. KEY RESULTS During morphine withdrawal we observed an enhancement of NA turnover in parallel with an increase in mean arterial blood pressure (MAP) and heart rate (HR) in wild-type mice. In addition, naloxone-precipitated morphine withdrawal induced an activation of HPA axis and Hsp27. The principal finding of the present study was that plasma ACTH and corticosterone levels, MB-COMT, S-COMT, NA turnover, and Hsp27 expression and activation observed during morphine withdrawal were significantly inhibited in the CRF1 receptor-knockout mice. CONCLUSION AND IMPLICATIONS Our results demonstrate that CRF/CRF1 receptor activation may contribute to stress-induced cardiovascular dysfunction after naloxone-precipitated morphine withdrawal and suggest that CRF/CRF1 receptor pathways could contribute to cardiovascular disease associated with opioid addiction.
The Scientific World Journal, 2002
Nebivolol is a new selective beta 1-adrenoceptor antagonist with nitric oxide (NO)releasing prope... more Nebivolol is a new selective beta 1-adrenoceptor antagonist with nitric oxide (NO)releasing properties. In the present study we have analyzed whether nebivolol affects the development of the arterial hypertension that follows the chronic inhibition of nitric oxide synthesis. Nebivolol (1 mg/kg/day, 14 days) was given concurrently with the NO synthesis inhibitor N w-nitro-L-arginine methyl ester (L-NAME, 0.1, 1, and 10 mg/kg/day, 14 days) to several groups of rats. Blood pressure, renal function, plasma renin activity (PRA), and NO activity and metabolites were measured at the end of the treatment period. L-NAME treatment alone increased mean arterial pressure dose dependently (103.5 ± 2.4, 110.9 ± 2.0, and 125.8 ± 2.2 mmHg, respectively). Nebivolol completely prevented the development of arterial hypertension in the groups treated with L-NAME at the doses of 0.1 and 1 mg/kg/day and reduced the increase achieved with the L-NAME dose of 10 mg/kg/day (110.3 ± 2.7). There were no differences in glomerular filtration rate or natriuresis between nebivolol-treated and-untreated rats. Plasma nitrates+nitrites and calcium-dependent NO synthase activity in the kidney also decreased dose dependently with L-NAME treatment and nebivolol did not significantly modify it. However, PRA was lower in all groups treated with nebivolol and L-NAME as compared to the rats receiving only L-NAME. These data indicate that nebivolol prevents the development of the arterial hypertension associated with chronic NO deficit and this effect seems to be dependent on the inhibition of renin-angiotensin system.
International Journal of Molecular Sciences, Jun 30, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Página Web: http://www.um.es/\~grupo-cirrosis/index.html Una de las más importantes característica... more Página Web: http://www.um.es/~grupo-cirrosis/index.html Una de las más importantes características de la cirrosis hepática, sea humana o experimental, es la vasodilatación esplácnica y sistémica. Aunque su origen no está en absoluto claro, se piensa que además de factores como el aumento de la capacidad vascular, hay también una mayor vasodilatación activa, como consecuencia de la excesiva generación de sustancias vasodilatadoras, muchas de ellas de origen local. De entre la gran variedad de sustancias implicadas, en este trabajo analizaremos algunas de las pruebas que indican que el óxido nítrico (NO) es el principal factor implicado en dicha vasodilatación. El NO en la pared vascular. El NO se forma a partir del aminoácido L-arginina (1-3), debido a la acción de varias isoformas del enzima óxido nítrico sintasa (NOS). La isoforma endotelial o NOS3 se expresa de forma constitutiva en la célula endotelial, donde hace que se forme NO de manera continua, aunque en pequeñas cantidades, en respuesta a factores físicos (estrés de rozamiento) o químicos (hormonas vasoconstrictoras, por ejemplo). Por el contrario, la NOS2 o inducible es "inducida" en la pared vascular por endotoxinas y citoquinas, entre otros, y produce grandes cantidades de NO, bien que en un corto espacio de tiempo. Este proceso produce una gran vasodilatación que juega un papel de gran importancia en la regulación del proceso inflamatorio. La vasodilatación debida al NO requiere la producción de un segundo mensajero, el cGMP, como se demuestra tras la inhibición de la guanilato ciclasa mediante azul de metileno, por ejemplo. A su vez, el cGMP produce la vasodilatación mediante la
American Journal of Physiology-regulatory Integrative and Comparative Physiology, Dec 1, 1994
In the present study, we have characterized the renal response to inhibition of endogenous nitric... more In the present study, we have characterized the renal response to inhibition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period, whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR increased UV and UNaV significantly by the 1st h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These effects were prevented by pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an important mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.
Hypertension, Mar 1, 1996
The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has ... more The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has been studied in anesthetized Munich-Wistar rats by use of laser Doppler flowmeter. Acute administration of N ω -nitro- l -arginine methyl ester (L-NAME) 10 mg/kg IV (n=8) increased mean arterial pressure by 27.8±3.6%, decreased papillary blood flow by 39.4±3.8%, and decreased renal blood flow by 47.4±1.9%. The subsequent administration of indomethacin (7.5 mg/kg IV) further decreased papillary blood flow (35.2±2.5%) without significant changes in mean arterial pressure or renal blood flow. In a second group (n=6), administration of indomethacin before L-NAME decreased papillary blood flow by 39.6±2.1% without significantly altering mean arterial pressure or renal blood flow. The subsequent injection of L-NAME further decreased papillary blood flow (32.9±1.8%) and renal blood flow (49.8±6.6%) while increasing mean arterial pressure to a level not significantly different from that found in the first group. Autoregulation studies showed that L-NAME but not indomethacin reduced the renal perfusion pressure–renal blood flow relationship without altering autoregulation. However, both nitric oxide and prostaglandins importantly affected the renal perfusion pressure–papillary blood flow relationship because L-NAME and indomethacin significantly decreased this relationship in an additive fashion. Although both drugs reduced the sensitivity of the pressure–papillary flow relationship, only L-NAME affected autoregulation so that papillary blood flow was autoregulated at higher renal perfusion pressures. Thus, the present results indicate that both nitric oxide and prostaglandins control a similar percentage of rat renal papillary blood flow, but nitric oxide seems to be more important than prostaglandins as a mediator of the pressure–blood flow relationship. In contrast, only nitric oxide modifies the renal blood flow level, although it does not disturb whole-kidney blood flow autoregulation.
Clinical Science, Jan 17, 2006
The present study investigates the effects of chronic administration of ACEIs (angiotensin-conver... more The present study investigates the effects of chronic administration of ACEIs (angiotensin-converting-enzyme inhibitors; either zofenopril or enalapril) in combination with a diruetic (hydrochlorothiazide) on BP (blood pressure) increase and renal injury induced by L-NAME (N Gnitro-L-arginine methyl ester), an inhibitor of NO (nitric oxide) synthesis. Rats were untreated or received L-NAME alone, L-NAME + zofenopril + hydrochlorothiazide or L-NAME + enalapril + hydrochlorothiazide for 8 weeks. L-NAME treatment resulted in marked elevation in BP and mortality. Treatment with either ACEI and diuretic prevented the increase in BP induced by L-NAME, reduced the death rate and improved excretory parameters. Renal injury in the L-NAME group was severe, but, in the groups treated with either ACEI and diuretic, glomerular and tubulointerstitial lesions were not observed and the intensity, number and size of vessels affected was reduced. However, the efficacy of zofenopril + diuretic was superior to that of enalapril + diuretic in reducing vascular alterations. Oxidative stress indices and the expression of NO synthase and nitrotyrosine were normalized by the treatments. In conclusion, the combined treatment of zofenopril or enalapril with hydrochlorothiazide completely prevented the development of arterial hypertension induced by L-NAME. Renal morphological and functional alterations in the hypertensive animals were also almost completely normalized, but the treatment with zofenopril + diuretic produced a more complete organ protection. The protective effect is related to an activation of endothelial NO synthase expression and to a normalization of the oxidative stress parameters due to the inhibition of angiotensin II.
Platelets, Feb 2, 2017
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an ... more Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model. The effect of chronic folic acid treatment was also analyzed. Acute treatment with HCY increased the aggregation response to ADP and calcium responses to thrombin in platelets of control and BDL rats. Capacitative calcium entry was not altered by HCY. Chronic treatment with folic acid decreased platelet aggregation in control and BDL rats, but this decrease was greater in BDL rats. In folic acid-treated rats, thrombininduced calcium entry and release were decreased in platelet of control rats but unaltered in BDL rats; however, capacitative calcium entry was decreased in platelets of control and BDL rats treated with folic acid. Reactive oxygen species were produced at higher levels by BDL platelets after stimulation with HCY or thrombin and folic acid normalized these responses. HCY plays a role in the enhanced platelet aggregation response of BDL rats, probably through an enhanced formation of ROS. Folic acid pretreatment normalizes many of the platelet alterations shown by BDL rats.
American Journal of Physiology-endocrinology and Metabolism, May 1, 1995
Previous studies have indicated that the pressure diuresis and natriuresis (PDN) response is grea... more Previous studies have indicated that the pressure diuresis and natriuresis (PDN) response is greatly impaired in thyroxine-treated hypertensive rats. In the present study, we have examined the role of the renin angiotensin system (RAS) as a mediator of these alterations by characterizing the relationships between renal perfusion pressure and urine flow and sodium excretion in hyperthyroid rats acutely treated with a converting-enzyme inhibitor (captopril, 2 mg/kg) or an AT1 angiotensin II receptor blocker (losartan, 10 mg/kg). In the control animals, captopril did not change mean arterial pressure (MAP) or renal blood flow (RBF) but significantly decreased MAP and increased RBF and glomerular filtration rate in the hyperthyroid rats. Captopril did not change the PDN response of the control animals but improved significantly that of the hyperthyroid rats, although it was not completely normalized. Losartan also significantly improved renal hemodynamics and excretion in hyperthyroid rats. These results indicate that an increased intrarenal activity of the RAS is partly responsible for the blunted renal PDN mechanism of the hyperthyroid rats.
Journal of Hypertension, Feb 1, 1999
Objective Chronic inhibition of nitric oxide synthesis has been shown to cause arterial hypertens... more Objective Chronic inhibition of nitric oxide synthesis has been shown to cause arterial hypertension and an important blunting of the pressure diuresis and natriuresis response. The mechanisms mediating these abnormalities are not completely established. We therefore studied the effects of endothelin on these alterations. Materials and methods Pressure diuretic and natriuretic relationships were evaluated in rats treated chronically (3 weeks) with the nitric oxide synthesis inhibitor N ù-nitro-Larginine methyl ester (L-NAME; 40 mg/kg per day), alone or in combination with bosentan sodium salt (acute treatment: 10 mg/kg, intravenously; chronic treatment: 10 mg/kg per day). Results Chronic treatment with L-NAME signi®cantly elevated mean arterial pressure (143.7 AE 2.8 mmHg versus 102.8 AE 1.6 in controls), reduced the glomerular ®ltration rate and renal blood¯ow and shifted the pressure diuretic and natriuretic responses to the right. Treatment with bosentan, either acute or chronically, did not attenuate the arterial hypertension of the L-NAME-treated rats but normalized the glomerular ®ltration rate and renal blood ow. In spite of the normalization of renal hemodynamics, the pressure diuretic and natriuretic responses of the bosentan-treated groups were not normalized, although chronic bosentan signi®cantly improved the pressure natriuretic response. Conclusions These results indicate that endothelin participates in the renal hemodynamic and excretory alterations that follow chronic inhibition of nitric oxide synthesis. However, the arterial hypertension is not mediated by endothelin activation.
Frontiers in Physiology, Jun 7, 2017
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an ... more Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model. Cholic acid (CA) or deoxycholic acid (DCA) did not change P-selectin expression or platelet aggregation in any group but elevated baseline platelet calcium levels. Incubation with both bile acids reduced calcium release after stimulation with thrombin in the absence of extracellular calcium. Pretreatment with CA but not with DCA reduced significantly thrombin-induced calcium entry in all three experimental groups. The capacitative calcium entry was also significantly lower in platelets pretreated with both bile acids. The simultaneous addition of thapsigargin and ionomycin to estimate the total amount of calcium in platelet internal stores was decreased by pretreatment with both CA and DCA, although these changes were significantly different in the control rats only with CA and in the BDL platelets with DCA. These results indicate that CA and DCA reduce calcium movements in platelets of control and BDL animals, thus suggesting that bile acids do not participate in the alterations observed in the BDL cirrotic model.
Clinical Science, Aug 1, 1993
1. The purpose of the present investigation was to determine whether an abnormality of the renal ... more 1. The purpose of the present investigation was to determine whether an abnormality of the renal papillary circulation is present in a well-established model of cirrhosis without ascites (carbon tetrachloride/phenobarbital). 2. Compared with the control animals, cirrhotic rats showed a reduced diuretic (61.0 +/- 5.1 versus 18.0 +/- 2.5%) and natriuretic (67.8 +/- 8.3 versus 29.6 +/- 3.6%) response to a volume expansion (3% body weight infusion of 0.9% NaCl). The volume expansion-induced increase in renal interstitial hydrostatic pressure was also blunted in the cirrhotic rats (control 9.3 +/- 0.9 versus cirrhotic 6.1 +/- 1.0 mmHg) and there were no differences in mean arterial blood pressure, renal blood flow or glomerular filtration rate between control and cirrhotic animals. 3. Papillary plasma flow was determined by the 125I-albumin accumulation technique and expressed as ml min-1 100 g-1. In the basal state, papillary plasma flow was significantly lower in cirrhotic rats (59.1 +/- 4.4, n = 9) than in the control animals (81.8 +/- 6.9, n = 9). An isotonic saline expansion similar to the one described above significantly increased papillary plasma flow in control rats (108.4 +/- 9.1, n = 7) but did not change it in cirrhotic rats (60.2 +/- 4.9, n = 6). 4. Our results indicate the existence of a selective alteration in the renal papillary circulation in cirrhotic rats, both in the basal state and after a well-established vasodilatory stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Educación Médica, Nov 1, 2018
EDUMED-221; No. of Pages 12 2 M.J. Cecilia et al. Diet; Alcohol; Drugs the population. To do this... more EDUMED-221; No. of Pages 12 2 M.J. Cecilia et al. Diet; Alcohol; Drugs the population. To do this, we have designed and validated questionnaire that evaluates the lifestyles of university students, and includes aspects such as socio-demographic characteristics, socioeconomic data, health status and quality of life, physical activity, tobacco, alcohol and other drugs, eating habits, and sexual behaviour. In general, the quality of life of the students is mostly good, although habits such as smoking or alcohol consumption show a clear tendency to worsen during the university stage. The questionnaire used could be a useful and reliable tool to identify unhealthy life habits or possible health problems.
I Jornadas Doctorales de la Universidad de Murcia, Jul 30, 2015
In liver cirrhosis, several haemostatic abnormalities occur, mostly episodes of bleeding, but the... more In liver cirrhosis, several haemostatic abnormalities occur, mostly episodes of bleeding, but there is a 9-20 % risk of thrombosis. Some extrinsic and intrinsic factors are altered in these patients and their role in the development of these alterations is not completely known.
Medical University, Sep 1, 2020
Introduction: Currently, the Doctor-Patient relationship of all cultures and societies is in cris... more Introduction: Currently, the Doctor-Patient relationship of all cultures and societies is in crisis due to the distrust that has arisen in this social contract. This distrust origins from various changes that have occurred worldwide. We, as doctors, can contribute to solving this crisis, reaffirming the values that integrate medical professionalism. In the absence of specific studies and programmes on medical professionalism in Spanish universities, we consider knowing the perception of medical professionalism by medical students at the University of Murcia essential to see if there is a need to introduce educational improvements in our faculty. Methods: A professionalism questionnaire from the Penn State University School of Medicine (PSCOM) was provided online, voluntarily and anonymously to all students of the Medicine degree of the University of Murcia. Results: The perception of professionalism in students was high, since all categories have more than 75% positive responses on average. The categories of Respect and Altruism were the best rated. On the other hand, there is a slight increase in negative responses as students progress through the degree. Between sexes, however, there were no differences in the criteria. Conclusions: Although the perception of professionalism is good, it is still a perception, so it should reach values closer to 100%. Therefore, the faculty is encouraged to carry out specific programmes to promote medical professionalism in the degree courses.
Educación Médica, Sep 1, 2018
Resumen La automedicación es la administración de medicamentos para aliviar un síntoma o curar un... more Resumen La automedicación es la administración de medicamentos para aliviar un síntoma o curar una enfermedad sin pasar por el control médico. Este comportamiento está muy extendido a nivel mundial, incluso dentro de la universidad en la que se forman los futuros profesionales que configurarán los servicios sanitarios de la comunidad. Aunque existen estudios relativos a las conductas de automedicación en la población universitaria en otros países, existen pocos datos relativos a este comportamiento en nuestro ámbito. El propósito de este estudio es estimar el nivel de automedicación en un colectivo universitario, así como los factores asociados a este comportamiento. El hábito de automedicación es muy frecuente en nuestra población de estudio, con una media de un 72,5%. Este valor va ascendiendo curso a curso desde un 53% en el primer curso de carrera hasta el 93% en el último. Casi el total de los alumnos admite la automedicación con analgésicos y es de destacar la automedicación con antibióticos (13,6%) utilizados para situaciones clínicas poco definidas. Más preocupante aún es la automedicación con medicamentos bajo receta regulada, como es el caso de los ansiolíticos y tranquilizantes, usado por un 5% de los estudiantes. Concluimos que el alto porcentaje de automedicación de la población general se ve prácticamente correspondido en esta población de estudiantes de Farmacia. Los medicamentos más consumidos son los analgésicos, antihistamínicos y antigripales; existen, además, porcentajes bajos pero notables de automedicación con antibióticos y ansiolíticos, lo que resulta más preocupante.
Educación Médica, 2021
En una mayoría de países, la educación médica es una especialidad médica más y preside la vida ac... more En una mayoría de países, la educación médica es una especialidad médica más y preside la vida académica en el grado, el posgrado y en la formación continuada. Pero la situación en España es muy mejorable. Aunque existe un creciente interés en la educación médica como disciplina o especialidad, la mayor parte de las facultades de Medicina españolas no disponen de una unidad o departamento de educación médica que se encargue del avance de la disciplina. Algunas facultades han dispuesto una unidad, cátedra, departamento o centro de estudios, adscrita o independiente a la dirección del centro, a veces sin relación orgánica alguna con el proceso de formación. En este artículo describiremos por qué creemos que estas estructuras son necesarias, su utilidad, así como sus funciones y el alcance de sus actividades. Analizaremos la situación actual en España con el ánimo de promocionar la creación de estas estructuras en todas las facultades de Medicina. Igualmente, repasaremos los mecanismos de los que se ha dotado a la formación especializada en el posgrado para dar respuestas a sus necesidades de formación. In a majority of countries, medical education is one more medical specialty and presides over academic life in undergraduate, graduate and continuing education. But, the situation in Spain is very improvable. Although there is a growing interest in medical education as a discipline or specialty, most of the Spanish faculties of Medicine do not have a unit or department of medical education, which is in charge of advancing the discipline. Some faculties have arranged a unit, chair, department or study center, attached or independent to the management of the center, sometimes without any organic relationship to the training process. In this article we will describe why we believe these structures are necessary, their usefulness, as well as their functions and the scope of their activities. We will analyze the current situation in Spain with the aim of promoting the creation of these structures in all the faculties of Medicine. We will also review the mechanisms that specialized postgraduate training has been equipped to provide answers to their training needs.
Consulta de difusión veterinaria, 2019
Clinical Case Reports, Jan 19, 2021
Our results do not support any effect of FVIII on platelet function in patients with severe HA tr... more Our results do not support any effect of FVIII on platelet function in patients with severe HA treated under the regime of prophylaxis.
British Journal of Pharmacology, Jan 13, 2014
The negative affective states of withdrawal involve the recruitment of brain and peripheral stres... more The negative affective states of withdrawal involve the recruitment of brain and peripheral stress circuitry [noradrenergic activity, induction of the hypothalamic-pituitary-adrenocortical (HPA) axis and activation of heat shock proteins (Hsps)]. Corticotropin-releasing factor (CRF) pathways are important mediators in the negative symptoms of opioid withdrawal. We performed a series of experiments to characterize the role of the CRF1 receptor in the response of stress systems to morphine withdrawal and its effect in the heart using genetically engineered mice lacking functional CRF1 receptors. EXPERIMENTAL APPROACH Wild-type and CRF1 receptor-knockout mice were treated with increasing doses of morphine. Precipitated withdrawal was induced by naloxone. Plasma adrenocorticotropic hormone (ACTH) and corticosterone levels, the expression of myocardial Hsp27, Hsp27 phosphorylated at Ser 82 , membrane (MB)-COMT, soluble (S)-COMT protein and NA turnover were evaluated by RIA, immunoblotting and HPLC. KEY RESULTS During morphine withdrawal we observed an enhancement of NA turnover in parallel with an increase in mean arterial blood pressure (MAP) and heart rate (HR) in wild-type mice. In addition, naloxone-precipitated morphine withdrawal induced an activation of HPA axis and Hsp27. The principal finding of the present study was that plasma ACTH and corticosterone levels, MB-COMT, S-COMT, NA turnover, and Hsp27 expression and activation observed during morphine withdrawal were significantly inhibited in the CRF1 receptor-knockout mice. CONCLUSION AND IMPLICATIONS Our results demonstrate that CRF/CRF1 receptor activation may contribute to stress-induced cardiovascular dysfunction after naloxone-precipitated morphine withdrawal and suggest that CRF/CRF1 receptor pathways could contribute to cardiovascular disease associated with opioid addiction.
The Scientific World Journal, 2002
Nebivolol is a new selective beta 1-adrenoceptor antagonist with nitric oxide (NO)releasing prope... more Nebivolol is a new selective beta 1-adrenoceptor antagonist with nitric oxide (NO)releasing properties. In the present study we have analyzed whether nebivolol affects the development of the arterial hypertension that follows the chronic inhibition of nitric oxide synthesis. Nebivolol (1 mg/kg/day, 14 days) was given concurrently with the NO synthesis inhibitor N w-nitro-L-arginine methyl ester (L-NAME, 0.1, 1, and 10 mg/kg/day, 14 days) to several groups of rats. Blood pressure, renal function, plasma renin activity (PRA), and NO activity and metabolites were measured at the end of the treatment period. L-NAME treatment alone increased mean arterial pressure dose dependently (103.5 ± 2.4, 110.9 ± 2.0, and 125.8 ± 2.2 mmHg, respectively). Nebivolol completely prevented the development of arterial hypertension in the groups treated with L-NAME at the doses of 0.1 and 1 mg/kg/day and reduced the increase achieved with the L-NAME dose of 10 mg/kg/day (110.3 ± 2.7). There were no differences in glomerular filtration rate or natriuresis between nebivolol-treated and-untreated rats. Plasma nitrates+nitrites and calcium-dependent NO synthase activity in the kidney also decreased dose dependently with L-NAME treatment and nebivolol did not significantly modify it. However, PRA was lower in all groups treated with nebivolol and L-NAME as compared to the rats receiving only L-NAME. These data indicate that nebivolol prevents the development of the arterial hypertension associated with chronic NO deficit and this effect seems to be dependent on the inhibition of renin-angiotensin system.
International Journal of Molecular Sciences, Jun 30, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Página Web: http://www.um.es/\~grupo-cirrosis/index.html Una de las más importantes característica... more Página Web: http://www.um.es/~grupo-cirrosis/index.html Una de las más importantes características de la cirrosis hepática, sea humana o experimental, es la vasodilatación esplácnica y sistémica. Aunque su origen no está en absoluto claro, se piensa que además de factores como el aumento de la capacidad vascular, hay también una mayor vasodilatación activa, como consecuencia de la excesiva generación de sustancias vasodilatadoras, muchas de ellas de origen local. De entre la gran variedad de sustancias implicadas, en este trabajo analizaremos algunas de las pruebas que indican que el óxido nítrico (NO) es el principal factor implicado en dicha vasodilatación. El NO en la pared vascular. El NO se forma a partir del aminoácido L-arginina (1-3), debido a la acción de varias isoformas del enzima óxido nítrico sintasa (NOS). La isoforma endotelial o NOS3 se expresa de forma constitutiva en la célula endotelial, donde hace que se forme NO de manera continua, aunque en pequeñas cantidades, en respuesta a factores físicos (estrés de rozamiento) o químicos (hormonas vasoconstrictoras, por ejemplo). Por el contrario, la NOS2 o inducible es "inducida" en la pared vascular por endotoxinas y citoquinas, entre otros, y produce grandes cantidades de NO, bien que en un corto espacio de tiempo. Este proceso produce una gran vasodilatación que juega un papel de gran importancia en la regulación del proceso inflamatorio. La vasodilatación debida al NO requiere la producción de un segundo mensajero, el cGMP, como se demuestra tras la inhibición de la guanilato ciclasa mediante azul de metileno, por ejemplo. A su vez, el cGMP produce la vasodilatación mediante la
American Journal of Physiology-regulatory Integrative and Comparative Physiology, Dec 1, 1994
In the present study, we have characterized the renal response to inhibition of endogenous nitric... more In the present study, we have characterized the renal response to inhibition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period, whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR increased UV and UNaV significantly by the 1st h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These effects were prevented by pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an important mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.
Hypertension, Mar 1, 1996
The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has ... more The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has been studied in anesthetized Munich-Wistar rats by use of laser Doppler flowmeter. Acute administration of N ω -nitro- l -arginine methyl ester (L-NAME) 10 mg/kg IV (n=8) increased mean arterial pressure by 27.8±3.6%, decreased papillary blood flow by 39.4±3.8%, and decreased renal blood flow by 47.4±1.9%. The subsequent administration of indomethacin (7.5 mg/kg IV) further decreased papillary blood flow (35.2±2.5%) without significant changes in mean arterial pressure or renal blood flow. In a second group (n=6), administration of indomethacin before L-NAME decreased papillary blood flow by 39.6±2.1% without significantly altering mean arterial pressure or renal blood flow. The subsequent injection of L-NAME further decreased papillary blood flow (32.9±1.8%) and renal blood flow (49.8±6.6%) while increasing mean arterial pressure to a level not significantly different from that found in the first group. Autoregulation studies showed that L-NAME but not indomethacin reduced the renal perfusion pressure–renal blood flow relationship without altering autoregulation. However, both nitric oxide and prostaglandins importantly affected the renal perfusion pressure–papillary blood flow relationship because L-NAME and indomethacin significantly decreased this relationship in an additive fashion. Although both drugs reduced the sensitivity of the pressure–papillary flow relationship, only L-NAME affected autoregulation so that papillary blood flow was autoregulated at higher renal perfusion pressures. Thus, the present results indicate that both nitric oxide and prostaglandins control a similar percentage of rat renal papillary blood flow, but nitric oxide seems to be more important than prostaglandins as a mediator of the pressure–blood flow relationship. In contrast, only nitric oxide modifies the renal blood flow level, although it does not disturb whole-kidney blood flow autoregulation.
Clinical Science, Jan 17, 2006
The present study investigates the effects of chronic administration of ACEIs (angiotensin-conver... more The present study investigates the effects of chronic administration of ACEIs (angiotensin-converting-enzyme inhibitors; either zofenopril or enalapril) in combination with a diruetic (hydrochlorothiazide) on BP (blood pressure) increase and renal injury induced by L-NAME (N Gnitro-L-arginine methyl ester), an inhibitor of NO (nitric oxide) synthesis. Rats were untreated or received L-NAME alone, L-NAME + zofenopril + hydrochlorothiazide or L-NAME + enalapril + hydrochlorothiazide for 8 weeks. L-NAME treatment resulted in marked elevation in BP and mortality. Treatment with either ACEI and diuretic prevented the increase in BP induced by L-NAME, reduced the death rate and improved excretory parameters. Renal injury in the L-NAME group was severe, but, in the groups treated with either ACEI and diuretic, glomerular and tubulointerstitial lesions were not observed and the intensity, number and size of vessels affected was reduced. However, the efficacy of zofenopril + diuretic was superior to that of enalapril + diuretic in reducing vascular alterations. Oxidative stress indices and the expression of NO synthase and nitrotyrosine were normalized by the treatments. In conclusion, the combined treatment of zofenopril or enalapril with hydrochlorothiazide completely prevented the development of arterial hypertension induced by L-NAME. Renal morphological and functional alterations in the hypertensive animals were also almost completely normalized, but the treatment with zofenopril + diuretic produced a more complete organ protection. The protective effect is related to an activation of endothelial NO synthase expression and to a normalization of the oxidative stress parameters due to the inhibition of angiotensin II.
Platelets, Feb 2, 2017
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an ... more Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model. The effect of chronic folic acid treatment was also analyzed. Acute treatment with HCY increased the aggregation response to ADP and calcium responses to thrombin in platelets of control and BDL rats. Capacitative calcium entry was not altered by HCY. Chronic treatment with folic acid decreased platelet aggregation in control and BDL rats, but this decrease was greater in BDL rats. In folic acid-treated rats, thrombininduced calcium entry and release were decreased in platelet of control rats but unaltered in BDL rats; however, capacitative calcium entry was decreased in platelets of control and BDL rats treated with folic acid. Reactive oxygen species were produced at higher levels by BDL platelets after stimulation with HCY or thrombin and folic acid normalized these responses. HCY plays a role in the enhanced platelet aggregation response of BDL rats, probably through an enhanced formation of ROS. Folic acid pretreatment normalizes many of the platelet alterations shown by BDL rats.
American Journal of Physiology-endocrinology and Metabolism, May 1, 1995
Previous studies have indicated that the pressure diuresis and natriuresis (PDN) response is grea... more Previous studies have indicated that the pressure diuresis and natriuresis (PDN) response is greatly impaired in thyroxine-treated hypertensive rats. In the present study, we have examined the role of the renin angiotensin system (RAS) as a mediator of these alterations by characterizing the relationships between renal perfusion pressure and urine flow and sodium excretion in hyperthyroid rats acutely treated with a converting-enzyme inhibitor (captopril, 2 mg/kg) or an AT1 angiotensin II receptor blocker (losartan, 10 mg/kg). In the control animals, captopril did not change mean arterial pressure (MAP) or renal blood flow (RBF) but significantly decreased MAP and increased RBF and glomerular filtration rate in the hyperthyroid rats. Captopril did not change the PDN response of the control animals but improved significantly that of the hyperthyroid rats, although it was not completely normalized. Losartan also significantly improved renal hemodynamics and excretion in hyperthyroid rats. These results indicate that an increased intrarenal activity of the RAS is partly responsible for the blunted renal PDN mechanism of the hyperthyroid rats.
Journal of Hypertension, Feb 1, 1999
Objective Chronic inhibition of nitric oxide synthesis has been shown to cause arterial hypertens... more Objective Chronic inhibition of nitric oxide synthesis has been shown to cause arterial hypertension and an important blunting of the pressure diuresis and natriuresis response. The mechanisms mediating these abnormalities are not completely established. We therefore studied the effects of endothelin on these alterations. Materials and methods Pressure diuretic and natriuretic relationships were evaluated in rats treated chronically (3 weeks) with the nitric oxide synthesis inhibitor N ù-nitro-Larginine methyl ester (L-NAME; 40 mg/kg per day), alone or in combination with bosentan sodium salt (acute treatment: 10 mg/kg, intravenously; chronic treatment: 10 mg/kg per day). Results Chronic treatment with L-NAME signi®cantly elevated mean arterial pressure (143.7 AE 2.8 mmHg versus 102.8 AE 1.6 in controls), reduced the glomerular ®ltration rate and renal blood¯ow and shifted the pressure diuretic and natriuretic responses to the right. Treatment with bosentan, either acute or chronically, did not attenuate the arterial hypertension of the L-NAME-treated rats but normalized the glomerular ®ltration rate and renal blood ow. In spite of the normalization of renal hemodynamics, the pressure diuretic and natriuretic responses of the bosentan-treated groups were not normalized, although chronic bosentan signi®cantly improved the pressure natriuretic response. Conclusions These results indicate that endothelin participates in the renal hemodynamic and excretory alterations that follow chronic inhibition of nitric oxide synthesis. However, the arterial hypertension is not mediated by endothelin activation.
Frontiers in Physiology, Jun 7, 2017
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an ... more Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model. Cholic acid (CA) or deoxycholic acid (DCA) did not change P-selectin expression or platelet aggregation in any group but elevated baseline platelet calcium levels. Incubation with both bile acids reduced calcium release after stimulation with thrombin in the absence of extracellular calcium. Pretreatment with CA but not with DCA reduced significantly thrombin-induced calcium entry in all three experimental groups. The capacitative calcium entry was also significantly lower in platelets pretreated with both bile acids. The simultaneous addition of thapsigargin and ionomycin to estimate the total amount of calcium in platelet internal stores was decreased by pretreatment with both CA and DCA, although these changes were significantly different in the control rats only with CA and in the BDL platelets with DCA. These results indicate that CA and DCA reduce calcium movements in platelets of control and BDL animals, thus suggesting that bile acids do not participate in the alterations observed in the BDL cirrotic model.
Clinical Science, Aug 1, 1993
1. The purpose of the present investigation was to determine whether an abnormality of the renal ... more 1. The purpose of the present investigation was to determine whether an abnormality of the renal papillary circulation is present in a well-established model of cirrhosis without ascites (carbon tetrachloride/phenobarbital). 2. Compared with the control animals, cirrhotic rats showed a reduced diuretic (61.0 +/- 5.1 versus 18.0 +/- 2.5%) and natriuretic (67.8 +/- 8.3 versus 29.6 +/- 3.6%) response to a volume expansion (3% body weight infusion of 0.9% NaCl). The volume expansion-induced increase in renal interstitial hydrostatic pressure was also blunted in the cirrhotic rats (control 9.3 +/- 0.9 versus cirrhotic 6.1 +/- 1.0 mmHg) and there were no differences in mean arterial blood pressure, renal blood flow or glomerular filtration rate between control and cirrhotic animals. 3. Papillary plasma flow was determined by the 125I-albumin accumulation technique and expressed as ml min-1 100 g-1. In the basal state, papillary plasma flow was significantly lower in cirrhotic rats (59.1 +/- 4.4, n = 9) than in the control animals (81.8 +/- 6.9, n = 9). An isotonic saline expansion similar to the one described above significantly increased papillary plasma flow in control rats (108.4 +/- 9.1, n = 7) but did not change it in cirrhotic rats (60.2 +/- 4.9, n = 6). 4. Our results indicate the existence of a selective alteration in the renal papillary circulation in cirrhotic rats, both in the basal state and after a well-established vasodilatory stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Educación Médica, Nov 1, 2018
EDUMED-221; No. of Pages 12 2 M.J. Cecilia et al. Diet; Alcohol; Drugs the population. To do this... more EDUMED-221; No. of Pages 12 2 M.J. Cecilia et al. Diet; Alcohol; Drugs the population. To do this, we have designed and validated questionnaire that evaluates the lifestyles of university students, and includes aspects such as socio-demographic characteristics, socioeconomic data, health status and quality of life, physical activity, tobacco, alcohol and other drugs, eating habits, and sexual behaviour. In general, the quality of life of the students is mostly good, although habits such as smoking or alcohol consumption show a clear tendency to worsen during the university stage. The questionnaire used could be a useful and reliable tool to identify unhealthy life habits or possible health problems.
I Jornadas Doctorales de la Universidad de Murcia, Jul 30, 2015
In liver cirrhosis, several haemostatic abnormalities occur, mostly episodes of bleeding, but the... more In liver cirrhosis, several haemostatic abnormalities occur, mostly episodes of bleeding, but there is a 9-20 % risk of thrombosis. Some extrinsic and intrinsic factors are altered in these patients and their role in the development of these alterations is not completely known.
Medical University, Sep 1, 2020
Introduction: Currently, the Doctor-Patient relationship of all cultures and societies is in cris... more Introduction: Currently, the Doctor-Patient relationship of all cultures and societies is in crisis due to the distrust that has arisen in this social contract. This distrust origins from various changes that have occurred worldwide. We, as doctors, can contribute to solving this crisis, reaffirming the values that integrate medical professionalism. In the absence of specific studies and programmes on medical professionalism in Spanish universities, we consider knowing the perception of medical professionalism by medical students at the University of Murcia essential to see if there is a need to introduce educational improvements in our faculty. Methods: A professionalism questionnaire from the Penn State University School of Medicine (PSCOM) was provided online, voluntarily and anonymously to all students of the Medicine degree of the University of Murcia. Results: The perception of professionalism in students was high, since all categories have more than 75% positive responses on average. The categories of Respect and Altruism were the best rated. On the other hand, there is a slight increase in negative responses as students progress through the degree. Between sexes, however, there were no differences in the criteria. Conclusions: Although the perception of professionalism is good, it is still a perception, so it should reach values closer to 100%. Therefore, the faculty is encouraged to carry out specific programmes to promote medical professionalism in the degree courses.
Educación Médica, Sep 1, 2018
Resumen La automedicación es la administración de medicamentos para aliviar un síntoma o curar un... more Resumen La automedicación es la administración de medicamentos para aliviar un síntoma o curar una enfermedad sin pasar por el control médico. Este comportamiento está muy extendido a nivel mundial, incluso dentro de la universidad en la que se forman los futuros profesionales que configurarán los servicios sanitarios de la comunidad. Aunque existen estudios relativos a las conductas de automedicación en la población universitaria en otros países, existen pocos datos relativos a este comportamiento en nuestro ámbito. El propósito de este estudio es estimar el nivel de automedicación en un colectivo universitario, así como los factores asociados a este comportamiento. El hábito de automedicación es muy frecuente en nuestra población de estudio, con una media de un 72,5%. Este valor va ascendiendo curso a curso desde un 53% en el primer curso de carrera hasta el 93% en el último. Casi el total de los alumnos admite la automedicación con analgésicos y es de destacar la automedicación con antibióticos (13,6%) utilizados para situaciones clínicas poco definidas. Más preocupante aún es la automedicación con medicamentos bajo receta regulada, como es el caso de los ansiolíticos y tranquilizantes, usado por un 5% de los estudiantes. Concluimos que el alto porcentaje de automedicación de la población general se ve prácticamente correspondido en esta población de estudiantes de Farmacia. Los medicamentos más consumidos son los analgésicos, antihistamínicos y antigripales; existen, además, porcentajes bajos pero notables de automedicación con antibióticos y ansiolíticos, lo que resulta más preocupante.
Educación Médica, 2021
En una mayoría de países, la educación médica es una especialidad médica más y preside la vida ac... more En una mayoría de países, la educación médica es una especialidad médica más y preside la vida académica en el grado, el posgrado y en la formación continuada. Pero la situación en España es muy mejorable. Aunque existe un creciente interés en la educación médica como disciplina o especialidad, la mayor parte de las facultades de Medicina españolas no disponen de una unidad o departamento de educación médica que se encargue del avance de la disciplina. Algunas facultades han dispuesto una unidad, cátedra, departamento o centro de estudios, adscrita o independiente a la dirección del centro, a veces sin relación orgánica alguna con el proceso de formación. En este artículo describiremos por qué creemos que estas estructuras son necesarias, su utilidad, así como sus funciones y el alcance de sus actividades. Analizaremos la situación actual en España con el ánimo de promocionar la creación de estas estructuras en todas las facultades de Medicina. Igualmente, repasaremos los mecanismos de los que se ha dotado a la formación especializada en el posgrado para dar respuestas a sus necesidades de formación. In a majority of countries, medical education is one more medical specialty and presides over academic life in undergraduate, graduate and continuing education. But, the situation in Spain is very improvable. Although there is a growing interest in medical education as a discipline or specialty, most of the Spanish faculties of Medicine do not have a unit or department of medical education, which is in charge of advancing the discipline. Some faculties have arranged a unit, chair, department or study center, attached or independent to the management of the center, sometimes without any organic relationship to the training process. In this article we will describe why we believe these structures are necessary, their usefulness, as well as their functions and the scope of their activities. We will analyze the current situation in Spain with the aim of promoting the creation of these structures in all the faculties of Medicine. We will also review the mechanisms that specialized postgraduate training has been equipped to provide answers to their training needs.
Consulta de difusión veterinaria, 2019