cristina arranz - Academia.edu (original) (raw)
Papers by cristina arranz
Journal of Science, Humanities and Arts - JOSHA, 2015
Journal of Science, Humanities and Arts - JOSHA, 2016
American Journal of Physiology-Heart and Circulatory Physiology, 2009
The objective was to study atrial natriuretic peptide (ANP) effects on mean arterial pressure (MA... more The objective was to study atrial natriuretic peptide (ANP) effects on mean arterial pressure (MAP) and cardiovascular nitric oxide (NO) system in spontaneously hypertensive rats (SHRs), investigating the receptors and signaling pathways involved. In vivo, SHRs and Wistar-Kyoto (WKY) rats were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg−1·min−1) for 1 h. MAP and nitrites and nitrates excretion (NOx) were determined. NO synthase (NOS) activity and endothelial (eNOS), neuronal (nNOS) and inducible (iNOS) NOS expression were measured in the heart and aorta. In vitro, heart and aortic NOS activity induced by ANP was determined in the presence of iNOS and nNOS inhibitors, natriuretic peptide receptor (NPR)-A/B blocker, Gi protein, and calmodulin inhibitors. As a result, ANP diminished MAP and increased NOx in both groups. Cardiovascular NOS activity was higher in SHRs than in WKY rats. ANP increased NOS activity, but the activation was lower in SHRs than in WKY rats. ANP had no e...
The FASEB Journal
The aim was to evaluate early cardiovascular alterations in rats exposed to moderate zinc deficie... more The aim was to evaluate early cardiovascular alterations in rats exposed to moderate zinc deficiency during fetal life and lactation, and compare the effects in males (m) and females (f).Wistar rats received low (L,8 ppm) or control (C,30 ppm) zinc diet from pregnancy until offspring weaning (day 21). At 21 days, we evaluate mayor (MM) and minor (mM) myocyte diameter (μm); aortic intima (Ai), media (Am) and perivascular collagen (Ac) thickness (μm); cardiac (C) and aortic (A) nitric oxide synthase (NOS) activity (pmol Cit/g.tissue.min); cardiac thiobarbituric acid substances (Tbars, nmol/mg protein), glutathione (G, mg/g protein), glutathione peroxidase (GPX, μmol/min/mg protein), catalase (CAT, pmol/mg protein) and superoxide dismutase (SOD, U/mg protein) activity in Lm, Lf, Cm and Cf rats. Cm Lm Cf Lf MM 14±1 18±1* 15±1 15±1 mM 8,6±0,5 10,7±0,3* 9,4±0,5 10,1±0,3 Ai 23,3±0,2 18,3±0,1* 23,9±0,2 18,9±0,2† Am 280±2 298±2 287±3 280±2 Ac 16±1 24±1* 12±1 23±2† C NOS 249±5 205±5* 247±3 20...
Numerosos estudios sugieren que trastornos metabólicos y desequilibrios nutricionales durante la ... more Numerosos estudios sugieren que trastornos metabólicos y desequilibrios nutricionales durante la vida intrauterina pueden inducir adaptaciones que programen enfermedades cardiovasculares e hipertensión arterial. En trabajos previos mostramos que la restricción moderada de cinc durante la vida fetal, la lactancia y/o el crecimiento conduce al desarrollo de hipertensión arterial y disfunción renal en la adultez.
Nutrition, Metabolism and Cardiovascular Diseases
Advances in Nutrition, 2022
This review summarizes the latest findings, from animal models and clinical studies, regarding th... more This review summarizes the latest findings, from animal models and clinical studies, regarding the cardiovascular and metabolic consequences in adult life of zinc deficiency (ZD) during prenatal and early postnatal life. The effect of zinc supplementation (ZS) and new insights about sex differences in the phenotype and severity of cardiovascular and metabolic alterations are also discussed. Zinc has antioxidant, anti-inflammatory, and antiapoptotic properties and regulates the activity of enzymes involved in regulation of the metabolic, cardiovascular, and renal systems. Maternal ZD is associated with intrauterine growth restriction and low birth weight (LBW). Breast-fed preterm infants are at risk of ZD due to lower zinc uptake during fetal life and reduced gut absorption capacity. ZS is most likely to increase growth in preterm infants and survival in LBW infants in countries where ZD is prevalent. Studies performed in rats revealed that moderate ZD during prenatal and/or early po...
The FASEB Journal, Apr 1, 2015
Moderate zinc deficiency during fetal and postnatal growth programs cardiovascular dysfunction an... more Moderate zinc deficiency during fetal and postnatal growth programs cardiovascular dysfunction and hypertension. Male zinc deficient rats showed reduced left ventricular (LV) wall thickness and eje...
Argentine Journal of Cardiology, 2021
Background: Intrauterine growth restriction is an abnormal fetal development characterized by a f... more Background: Intrauterine growth restriction is an abnormal fetal development characterized by a fetal growth rate lower than thepotential genetic growth for the gestational age. This condition represents a major burden for public health systems, as it increasesshort and long-term morbidity and mortality in the offspring, particularly because of its association with the development of cardiovascularand metabolic disease in adult life.Objectives: The aim of the present study was to identify possible cardinal genes involved in intrauterine growth restriction associatedwith the development of obesity, hypertension and metabolic syndrome using bioinformatics tools.Methods: A total of 343 genes involved in the phenotypes of interest were obtained and 20 genes were identified as significantlyrelevant in the interaction network analysis. Specifically, four of these identified genes encode for growth factors or their receptors,VEGFA, PDGFRB, IGF1R and EGFR. We also identified genes related t...
Journal of the American Society of Nephrology : JASN, Jan 3, 2017
Compared with males, females have lower BP before age 60, blunted hypertensive response to angiot... more Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did. Compared with the proximal tubule of males, the proximal tubule of females had greater phosphorylation of Na(+)/H(+) exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant expression of Na(+)/Pi cotransporter 2, claudin-2, and aquaporin 1. These changes associated with less bicarbonate reabsorption and higher lithium clearance in females. The distal nephrons of females had a higher abunda...
PloS one, 2016
Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hyp... more Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hypertensive states is unclear, we hypothesized that impaired response of the nitric oxide system to CNP in spontaneously hypertensive rats (SHR) could affect vascular relaxation induced by the peptide in this model of hypertension, and that other endothelial systems or potassium channels opening could also be involved. We examined the effect of CNP on isolated SHR aortas, and the hindlimb vascular resistance (HVR) in response to CNP administration compared to normotensive rats. Aortas were mounted in an isometric organ bath and contracted with phenylephrine. CNP relaxed arteries in a concentration-dependent manner but was less potent in inducing relaxation in SHR. The action of CNP was diminished by removal of the endothelium, inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester, and inhibition of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-on...
![Research paper thumbnail of [OP.8C.09] Cardiovascular Risk Factors Programmed by Zinc Deficiency During Growth](https://attachments.academia-assets.com/111229139/thumbnails/1.jpg)
](Journal of Hypertension, 2016
Objective: Oxidative stress in the rostral ventrolateral medulla (RVLM), a sympathetic center in ... more Objective: Oxidative stress in the rostral ventrolateral medulla (RVLM), a sympathetic center in brainstem, was implicated in the regulation of sympathetic activity in various hypertensive models including SHRSP. To elucidate pathophysiological roles of oxidative stress in SHRSP, we constructed a new congenic strain (referred to as SP.MES) by introducing a mutated P22phox gene of the Matsumoto Eosinophilic Shinshu (MES) rat into SHRSP. Design and method: The null mutation of P22phox in the MES rat was introduced in SHRSP by the speed congenial method. An established congenial strain called SP.MES harbored a 1.4-Mbp chromosomal fragment including P22phox on the genetic background of SHRSP. Microinjection of glutamate (Glu) and other substances was performed using that stereotaxic method, and changes in blood pressure (BP) was monitored with an intraarterial cannulated probe. Oxidative stress in the brainstem was measured with the lucigenin method. BP changes under cold stress at 4 °C was monitored with the telemetry system. Results: The level of oxidative stress was signifi cantly reduced in the brainstem of SP.MES. Baseline BP was signifi cantly reduce as well in SP.MES than in SHRSP (188 ± 13 vs. 220 ± 13 mmHg). Further, the BP response to Glu microinjection into RVLM was signifi cantly lower in SP.MES than in SHRSP (24 ± 4 vs. 42 ± 6 mmHg). Tempol and losartan reduced the response to Glu signifi cantly in SHRSP, while these reagents failed to reduce it in SP.MES. BP response to cold stress was blunted in SP.MES when compared with SHRSP.
BMC Pharmacology and Toxicology, 2015
Revista Argentina De Cardiologia, 2005
RESUMEN En trabajos previos demostramos que la activación de la sintetasa de óxido nítrico (NOS) ... more RESUMEN En trabajos previos demostramos que la activación de la sintetasa de óxido nítrico (NOS) mediaría, al menos en parte, las acciones hipotensoras, diuréticas y natriuréticas del péptido natriurético auricular (ANP). El objetivo fue investigar el tipo de receptor natriurético y los mecanismos de señalización involucrados en la activación de la NOS en presencia de ANP. Se trabajó con aurícula, aorta y riñón de ratas Wistar macho, previamente sacrificadas por decapitación. En dichos tejidos se midió la actividad de la NOS (pmol L-[U14C] citrulina/g tejido) utilizando L-[U14C] arginina como sustrato. Tanto el ANP como el cANP(4-23) (agonista específico de receptores NPR-C) aumentaron la actividad de la NOS en todos los tejidos y este aumento fue mayor para el ANP en el riñón y la aorta y similar para ambos péptidos en la aurícula. Estos efectos fueron bloqueados por la nifedipina (bloqueante de canales de Ca 2+ tipo L). La inhibición de la proteína Gi 1-2 con toxina pertussis bloqueó el efecto del cANP sobre la enzima tanto en la aurícula y la arteria como en el riñón. En la aurícula, la activación de la NOS mediada por el ANP se debería a la interacción del péptido con el receptor natriurético NPR-C, mientras que en el riñón y en la aorta participarían además los receptores natriuréticos NPR-A y/o B. El ANP interactuaría con el receptor NPR-C acoplado a la vía de la proteína Gi, activando la NOS Ca 2+ dependiente.
Revista argentina de cardiología
Introducción: El péptido natriurético tipo C (CNP) ha cobrado relevancia por sus efectos sobre la... more Introducción: El péptido natriurético tipo C (CNP) ha cobrado relevancia por sus efectos sobre la regulación de la función y la morfología del corazón y los vasos sanguíneos. Previamente demostramos in vitro que el CNP incrementa la actividad del sistema del óxido nítrico (NO) en ratas espontáneamente hipertensas (SHR). Objetivo: Estudiar el efecto del tratamiento crónico con CNP sobre la presión arterial sistólica (PAS), la función cardíaca y vascular y el sistema del NO en ratas espontáneamente hipertensas y normotensas. Material y métodos: Se emplearon ratas Wistar macho de 12 semanas de edad normotensas y espontáneamente hipertensas. Los animales recibieron infusión crónica de solución salina o CNP (0,75 mg/hora/rata) durante 14 días mediante la implantación de bombas osmóticas subcutáneas. Se midió la PAS y se realizaron un electrocardiograma y un ecocardiograma. Se extrajeron el ventrículo izquierdo y la arteria aorta torácica y se determinó la actividad, con L-[U 14 C]-arginina, de la óxido nítrico sintasa (NOS) y se realizaron estudios de reactividad vascular. Resultados: La administración crónica de CNP disminuyó la PAS en las SHR. Se observó menor volumen minuto en las SHR y el CNP incrementó dicho volumen, en tanto que no indujo cambios en las ratas normotensas. En las SHR se observó un desequilibrio en las respuestas vasodilatadora y vasoconstrictora en la arteria aorta y el tratamiento con CNP mejoró la función vascular respecto de las ratas normotensas. En ambos tejidos, la actividad de la NOS fue mayor en las SHR y se incrementó con la infusión durante 14 días de CNP. Sin embargo, dicho incremento fue menor en las SHR. Conclusión: El CNP induce cambios a nivel cardiovascular y en el sistema del NO que podrían resultar beneficiosos en este modelo de hipertensión arterial.
American Journal of Hypertension, 2008
Nitric oxide (NO) is involved in the control of cardiovascular function in physiological conditio... more Nitric oxide (NO) is involved in the control of cardiovascular function in physiological conditions and in heart diseases. As the prototypical endothelium-derived relaxing factor, NO is a primary determinant of blood vessel tone and thrombogenicity. In the context of heart tissue, these functions themselves are sufficient to justify the growing interest in NO as a regulator of cardiac function. However, despite the extensive literature, the exact sites and nature of NO action in the heart are as yet uncertain, while the earlier hypothesis that all three genomic forms of NO synthase (NOS) are active in the heart, have given rise to several intriguing questions. The classic concepts linking heart function with NO are: (i) NO is a regulator of cardiac function through direct action on the myocardium, and also by indirect vascular-dependent mechanisms 1 and (ii) the three known genomic isoforms of NOS 2 are present and functionally active in the heart. Gonzales et al. 3 and Zaobornyj et al. 4 challenged the second concept and reported that NO is produced in physiological conditions in the myocardium in relevant quantities by two of the isoforms of NOS: (i) an isoenzyme located in the mitochondria, known as mitochondrial NOS (mtNOS) and (ii) an isoenzyme located in the cytosolic fraction, the endothelial NOS (eNOS). The mechanisms by which NO regulates heart contractility and contraction rate, and the relation between the heart cycle and diffusion of NO between mitochondria and cytosol are physiological processes that are only now beginning to be understood. In this paper we attempt to revisit the major concepts about the influence of NO on heart rate, with special focus on the role of mitochondrial NO.
Journal of Hypertension, 2010
The aim of the study was to evaluate the diagnostic value of deltaRI (side-to-side difference of ... more The aim of the study was to evaluate the diagnostic value of deltaRI (side-to-side difference of renal resistive index) in moderate to high grade renal artery stenosis (RAS) with respect to angiographic and hemodynamic measurements.
Journal of Hypertension, 2011
smoking history was recorded in 75%, out of which 39.3% of patients were active smokers and remai... more smoking history was recorded in 75%, out of which 39.3% of patients were active smokers and remaining 35.7% were passive smokers. Positive family history related to hypertension was present in all of the subjects (100%). Conclusions: IHN is the consequence of the renal damage in primary arterial hypertension, but the high percentage of presence of the other risk factors certainly has synergistic effect upon the rate of progression. In view of the fact that most of the risk factors are reversible, early prevention of risk factors is mandatory in the treatment of patients with arterial hypertension.
Journal of Science, Humanities and Arts - JOSHA, 2015
Journal of Science, Humanities and Arts - JOSHA, 2016
American Journal of Physiology-Heart and Circulatory Physiology, 2009
The objective was to study atrial natriuretic peptide (ANP) effects on mean arterial pressure (MA... more The objective was to study atrial natriuretic peptide (ANP) effects on mean arterial pressure (MAP) and cardiovascular nitric oxide (NO) system in spontaneously hypertensive rats (SHRs), investigating the receptors and signaling pathways involved. In vivo, SHRs and Wistar-Kyoto (WKY) rats were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg−1·min−1) for 1 h. MAP and nitrites and nitrates excretion (NOx) were determined. NO synthase (NOS) activity and endothelial (eNOS), neuronal (nNOS) and inducible (iNOS) NOS expression were measured in the heart and aorta. In vitro, heart and aortic NOS activity induced by ANP was determined in the presence of iNOS and nNOS inhibitors, natriuretic peptide receptor (NPR)-A/B blocker, Gi protein, and calmodulin inhibitors. As a result, ANP diminished MAP and increased NOx in both groups. Cardiovascular NOS activity was higher in SHRs than in WKY rats. ANP increased NOS activity, but the activation was lower in SHRs than in WKY rats. ANP had no e...
The FASEB Journal
The aim was to evaluate early cardiovascular alterations in rats exposed to moderate zinc deficie... more The aim was to evaluate early cardiovascular alterations in rats exposed to moderate zinc deficiency during fetal life and lactation, and compare the effects in males (m) and females (f).Wistar rats received low (L,8 ppm) or control (C,30 ppm) zinc diet from pregnancy until offspring weaning (day 21). At 21 days, we evaluate mayor (MM) and minor (mM) myocyte diameter (μm); aortic intima (Ai), media (Am) and perivascular collagen (Ac) thickness (μm); cardiac (C) and aortic (A) nitric oxide synthase (NOS) activity (pmol Cit/g.tissue.min); cardiac thiobarbituric acid substances (Tbars, nmol/mg protein), glutathione (G, mg/g protein), glutathione peroxidase (GPX, μmol/min/mg protein), catalase (CAT, pmol/mg protein) and superoxide dismutase (SOD, U/mg protein) activity in Lm, Lf, Cm and Cf rats. Cm Lm Cf Lf MM 14±1 18±1* 15±1 15±1 mM 8,6±0,5 10,7±0,3* 9,4±0,5 10,1±0,3 Ai 23,3±0,2 18,3±0,1* 23,9±0,2 18,9±0,2† Am 280±2 298±2 287±3 280±2 Ac 16±1 24±1* 12±1 23±2† C NOS 249±5 205±5* 247±3 20...
Numerosos estudios sugieren que trastornos metabólicos y desequilibrios nutricionales durante la ... more Numerosos estudios sugieren que trastornos metabólicos y desequilibrios nutricionales durante la vida intrauterina pueden inducir adaptaciones que programen enfermedades cardiovasculares e hipertensión arterial. En trabajos previos mostramos que la restricción moderada de cinc durante la vida fetal, la lactancia y/o el crecimiento conduce al desarrollo de hipertensión arterial y disfunción renal en la adultez.
Nutrition, Metabolism and Cardiovascular Diseases
Advances in Nutrition, 2022
This review summarizes the latest findings, from animal models and clinical studies, regarding th... more This review summarizes the latest findings, from animal models and clinical studies, regarding the cardiovascular and metabolic consequences in adult life of zinc deficiency (ZD) during prenatal and early postnatal life. The effect of zinc supplementation (ZS) and new insights about sex differences in the phenotype and severity of cardiovascular and metabolic alterations are also discussed. Zinc has antioxidant, anti-inflammatory, and antiapoptotic properties and regulates the activity of enzymes involved in regulation of the metabolic, cardiovascular, and renal systems. Maternal ZD is associated with intrauterine growth restriction and low birth weight (LBW). Breast-fed preterm infants are at risk of ZD due to lower zinc uptake during fetal life and reduced gut absorption capacity. ZS is most likely to increase growth in preterm infants and survival in LBW infants in countries where ZD is prevalent. Studies performed in rats revealed that moderate ZD during prenatal and/or early po...
The FASEB Journal, Apr 1, 2015
Moderate zinc deficiency during fetal and postnatal growth programs cardiovascular dysfunction an... more Moderate zinc deficiency during fetal and postnatal growth programs cardiovascular dysfunction and hypertension. Male zinc deficient rats showed reduced left ventricular (LV) wall thickness and eje...
Argentine Journal of Cardiology, 2021
Background: Intrauterine growth restriction is an abnormal fetal development characterized by a f... more Background: Intrauterine growth restriction is an abnormal fetal development characterized by a fetal growth rate lower than thepotential genetic growth for the gestational age. This condition represents a major burden for public health systems, as it increasesshort and long-term morbidity and mortality in the offspring, particularly because of its association with the development of cardiovascularand metabolic disease in adult life.Objectives: The aim of the present study was to identify possible cardinal genes involved in intrauterine growth restriction associatedwith the development of obesity, hypertension and metabolic syndrome using bioinformatics tools.Methods: A total of 343 genes involved in the phenotypes of interest were obtained and 20 genes were identified as significantlyrelevant in the interaction network analysis. Specifically, four of these identified genes encode for growth factors or their receptors,VEGFA, PDGFRB, IGF1R and EGFR. We also identified genes related t...
Journal of the American Society of Nephrology : JASN, Jan 3, 2017
Compared with males, females have lower BP before age 60, blunted hypertensive response to angiot... more Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did. Compared with the proximal tubule of males, the proximal tubule of females had greater phosphorylation of Na(+)/H(+) exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant expression of Na(+)/Pi cotransporter 2, claudin-2, and aquaporin 1. These changes associated with less bicarbonate reabsorption and higher lithium clearance in females. The distal nephrons of females had a higher abunda...
PloS one, 2016
Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hyp... more Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hypertensive states is unclear, we hypothesized that impaired response of the nitric oxide system to CNP in spontaneously hypertensive rats (SHR) could affect vascular relaxation induced by the peptide in this model of hypertension, and that other endothelial systems or potassium channels opening could also be involved. We examined the effect of CNP on isolated SHR aortas, and the hindlimb vascular resistance (HVR) in response to CNP administration compared to normotensive rats. Aortas were mounted in an isometric organ bath and contracted with phenylephrine. CNP relaxed arteries in a concentration-dependent manner but was less potent in inducing relaxation in SHR. The action of CNP was diminished by removal of the endothelium, inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester, and inhibition of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-on...
Journal of Hypertension, 2016
Objective: Oxidative stress in the rostral ventrolateral medulla (RVLM), a sympathetic center in ... more Objective: Oxidative stress in the rostral ventrolateral medulla (RVLM), a sympathetic center in brainstem, was implicated in the regulation of sympathetic activity in various hypertensive models including SHRSP. To elucidate pathophysiological roles of oxidative stress in SHRSP, we constructed a new congenic strain (referred to as SP.MES) by introducing a mutated P22phox gene of the Matsumoto Eosinophilic Shinshu (MES) rat into SHRSP. Design and method: The null mutation of P22phox in the MES rat was introduced in SHRSP by the speed congenial method. An established congenial strain called SP.MES harbored a 1.4-Mbp chromosomal fragment including P22phox on the genetic background of SHRSP. Microinjection of glutamate (Glu) and other substances was performed using that stereotaxic method, and changes in blood pressure (BP) was monitored with an intraarterial cannulated probe. Oxidative stress in the brainstem was measured with the lucigenin method. BP changes under cold stress at 4 °C was monitored with the telemetry system. Results: The level of oxidative stress was signifi cantly reduced in the brainstem of SP.MES. Baseline BP was signifi cantly reduce as well in SP.MES than in SHRSP (188 ± 13 vs. 220 ± 13 mmHg). Further, the BP response to Glu microinjection into RVLM was signifi cantly lower in SP.MES than in SHRSP (24 ± 4 vs. 42 ± 6 mmHg). Tempol and losartan reduced the response to Glu signifi cantly in SHRSP, while these reagents failed to reduce it in SP.MES. BP response to cold stress was blunted in SP.MES when compared with SHRSP.
BMC Pharmacology and Toxicology, 2015
Revista Argentina De Cardiologia, 2005
RESUMEN En trabajos previos demostramos que la activación de la sintetasa de óxido nítrico (NOS) ... more RESUMEN En trabajos previos demostramos que la activación de la sintetasa de óxido nítrico (NOS) mediaría, al menos en parte, las acciones hipotensoras, diuréticas y natriuréticas del péptido natriurético auricular (ANP). El objetivo fue investigar el tipo de receptor natriurético y los mecanismos de señalización involucrados en la activación de la NOS en presencia de ANP. Se trabajó con aurícula, aorta y riñón de ratas Wistar macho, previamente sacrificadas por decapitación. En dichos tejidos se midió la actividad de la NOS (pmol L-[U14C] citrulina/g tejido) utilizando L-[U14C] arginina como sustrato. Tanto el ANP como el cANP(4-23) (agonista específico de receptores NPR-C) aumentaron la actividad de la NOS en todos los tejidos y este aumento fue mayor para el ANP en el riñón y la aorta y similar para ambos péptidos en la aurícula. Estos efectos fueron bloqueados por la nifedipina (bloqueante de canales de Ca 2+ tipo L). La inhibición de la proteína Gi 1-2 con toxina pertussis bloqueó el efecto del cANP sobre la enzima tanto en la aurícula y la arteria como en el riñón. En la aurícula, la activación de la NOS mediada por el ANP se debería a la interacción del péptido con el receptor natriurético NPR-C, mientras que en el riñón y en la aorta participarían además los receptores natriuréticos NPR-A y/o B. El ANP interactuaría con el receptor NPR-C acoplado a la vía de la proteína Gi, activando la NOS Ca 2+ dependiente.
Revista argentina de cardiología
Introducción: El péptido natriurético tipo C (CNP) ha cobrado relevancia por sus efectos sobre la... more Introducción: El péptido natriurético tipo C (CNP) ha cobrado relevancia por sus efectos sobre la regulación de la función y la morfología del corazón y los vasos sanguíneos. Previamente demostramos in vitro que el CNP incrementa la actividad del sistema del óxido nítrico (NO) en ratas espontáneamente hipertensas (SHR). Objetivo: Estudiar el efecto del tratamiento crónico con CNP sobre la presión arterial sistólica (PAS), la función cardíaca y vascular y el sistema del NO en ratas espontáneamente hipertensas y normotensas. Material y métodos: Se emplearon ratas Wistar macho de 12 semanas de edad normotensas y espontáneamente hipertensas. Los animales recibieron infusión crónica de solución salina o CNP (0,75 mg/hora/rata) durante 14 días mediante la implantación de bombas osmóticas subcutáneas. Se midió la PAS y se realizaron un electrocardiograma y un ecocardiograma. Se extrajeron el ventrículo izquierdo y la arteria aorta torácica y se determinó la actividad, con L-[U 14 C]-arginina, de la óxido nítrico sintasa (NOS) y se realizaron estudios de reactividad vascular. Resultados: La administración crónica de CNP disminuyó la PAS en las SHR. Se observó menor volumen minuto en las SHR y el CNP incrementó dicho volumen, en tanto que no indujo cambios en las ratas normotensas. En las SHR se observó un desequilibrio en las respuestas vasodilatadora y vasoconstrictora en la arteria aorta y el tratamiento con CNP mejoró la función vascular respecto de las ratas normotensas. En ambos tejidos, la actividad de la NOS fue mayor en las SHR y se incrementó con la infusión durante 14 días de CNP. Sin embargo, dicho incremento fue menor en las SHR. Conclusión: El CNP induce cambios a nivel cardiovascular y en el sistema del NO que podrían resultar beneficiosos en este modelo de hipertensión arterial.
American Journal of Hypertension, 2008
Nitric oxide (NO) is involved in the control of cardiovascular function in physiological conditio... more Nitric oxide (NO) is involved in the control of cardiovascular function in physiological conditions and in heart diseases. As the prototypical endothelium-derived relaxing factor, NO is a primary determinant of blood vessel tone and thrombogenicity. In the context of heart tissue, these functions themselves are sufficient to justify the growing interest in NO as a regulator of cardiac function. However, despite the extensive literature, the exact sites and nature of NO action in the heart are as yet uncertain, while the earlier hypothesis that all three genomic forms of NO synthase (NOS) are active in the heart, have given rise to several intriguing questions. The classic concepts linking heart function with NO are: (i) NO is a regulator of cardiac function through direct action on the myocardium, and also by indirect vascular-dependent mechanisms 1 and (ii) the three known genomic isoforms of NOS 2 are present and functionally active in the heart. Gonzales et al. 3 and Zaobornyj et al. 4 challenged the second concept and reported that NO is produced in physiological conditions in the myocardium in relevant quantities by two of the isoforms of NOS: (i) an isoenzyme located in the mitochondria, known as mitochondrial NOS (mtNOS) and (ii) an isoenzyme located in the cytosolic fraction, the endothelial NOS (eNOS). The mechanisms by which NO regulates heart contractility and contraction rate, and the relation between the heart cycle and diffusion of NO between mitochondria and cytosol are physiological processes that are only now beginning to be understood. In this paper we attempt to revisit the major concepts about the influence of NO on heart rate, with special focus on the role of mitochondrial NO.
Journal of Hypertension, 2010
The aim of the study was to evaluate the diagnostic value of deltaRI (side-to-side difference of ... more The aim of the study was to evaluate the diagnostic value of deltaRI (side-to-side difference of renal resistive index) in moderate to high grade renal artery stenosis (RAS) with respect to angiographic and hemodynamic measurements.
Journal of Hypertension, 2011
smoking history was recorded in 75%, out of which 39.3% of patients were active smokers and remai... more smoking history was recorded in 75%, out of which 39.3% of patients were active smokers and remaining 35.7% were passive smokers. Positive family history related to hypertension was present in all of the subjects (100%). Conclusions: IHN is the consequence of the renal damage in primary arterial hypertension, but the high percentage of presence of the other risk factors certainly has synergistic effect upon the rate of progression. In view of the fact that most of the risk factors are reversible, early prevention of risk factors is mandatory in the treatment of patients with arterial hypertension.