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Papers by Victor Pulgar

Cannabis and cannabinoid research, Apr 3, 2023

Objectives: To investigate the role of COX-derived prostanoids and the endocannabinoids 2-arachid... more Objectives: To investigate the role of COX-derived prostanoids and the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) on uterine vascular control during early pregnancy in a rodent model of preeclampsia. Methods: The transgenic female rat containing the human angiotensinogen (hAGN) gene mated with the male transgenic containing human renin (hREN) is a model of preeclampsia (TgA). Uterine arteries (UA) were isolated from Sprague–Dawley (SD, n =7) and TgA (n = 9) rats at 7 days of gestation and mounted in a wire myograph (DMT-USA, 620 M). Concentration response curves were performed in control conditions and after preincubation with indomethacin (Indo, 10^-5M), or inhibitors of endocannabinoid hydrolysis: URB597 (FAAH) or JZL184 (MAGL) at 10^-6 M. Data were fitted to a dose response curve, maximal responses were expressed as percent of maximal response to 75mM KCl (% KMAX) and sensitivity as pD2 (pD2 =-Log[EC50]). Results: Responses to ACh reached similar maximal relaxations (64± 8 vs. 75± 6%, p \u3e0.05), an increased contraction in TgA UA at ACh \u3e10lM was eliminated by Indo. Contraction to Phe was similar in both groups with an inhibitory effect of Indo in TgA UA (p Conclusions: Blockade of COX enzymes inhibited ACh, Phe and Ang II contractions whereas endogenous AEA and 2-AG reduced TgA UA Ang II contraction. A pro-contractile role of COX-derived mediators and a counteracting role of AEA and 2-AG in the enhanced Ang II contraction in TgA UA are evident before the hypertensive phenotype is established. These interactions may control uterine vascular function in early stages of preeclampsia

Hypertension, 2014

Intrauterine fetal growth restriction (IUGR), one of the serious complications of pregnancy, incr... more Intrauterine fetal growth restriction (IUGR), one of the serious complications of pregnancy, increases the risk for perinatal morbidity and mortality, and cardiovascular and renal abnormalities later in life. The components of the renin-angiotensin system (RAS) are important mediators of uteroplacental vasculature during pregnancy. The distribution of angiotensin converting enzyme 2 (ACE2), a key enzyme of the RAS, is described in the invading and intravascular trophoblasts, decidual cells and in the umbilical cord. Deletion of ACE2 restricts fetal weight gain and reduces fetal-to-placental weights ratio. ACE2 deficiency results in augmented uterine artery contractility to Ang II at mid-gestation. In this study we determined whether uterine artery dysfunction is associated with placental abnormalities in ACE2 KO mice at mid-gestation. Systolic blood pressures were higher in pregnant ACE2 KO vs. C57BL/6 wild type (WT) (102.3±5.1 vs. 85.1±1.9 mmHg). Urinary protein excretion, serum cr...

Hypertension, 2014

Both the renin-angiotensin (RAS) and endocannabinoid (ECS) systems are down-regulated at the earl... more Both the renin-angiotensin (RAS) and endocannabinoid (ECS) systems are down-regulated at the early stages of normal pregnancy. The striking similarity of the pattern of distribution of the two systems and their required down-regulation in early events of pregnancy make a compelling argument to compare their regulation in the early events of pregnancy in an animal that has placental activation of the RAS at l ate gestation. Female transgenic rats with overexpression of human (h) angiotensinogen were mated with male rats with h renin [Preeclamptic model (PRE)]. At day 7 of gestation, normal pregnant Sprague Dawley (SD) and PRE animals were anesthetized and bovine serum albumin (BSA) conjugated to Alexa Fluor 488 was injected systemically to assess uterine permeability in the implantation (IS) and interimplantation (IIS) uterine sites. Mean blood pressures were not different between SD and PRE animals (98.8±2 vs 97±3 mmHg, p>0.05). Uterine permeability measured as the IS/IIS ratio o...

Hypertension, 2012

Fetal growth restriction (FGR) remains a leading cause of perinatal morbidity and mortality in hu... more Fetal growth restriction (FGR) remains a leading cause of perinatal morbidity and mortality in humans. Angiotensin converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system that influences the balance between angiotensin II (Ang II) and angiotensin-(1-7) (Ang-(1-7)). ACE2 is highly expressed in the human placenta and maternal stromal tissue in normal pregnancy; however its role in pregnancy is not well understood. Our previous studies revealed that pregnancy in ACE2-deficient mice (ACE2KO) is associated with restricted maternal and fetal weight, attenuated circulating Ang-(1-7), and increased placental Ang II at the end of pregnancy. Since the loss of ACE2 may lead to vascular dysfunction and FGR, we compared the uterine artery reactivity in ACE2KO versus wild-type C57Bl/6 (WT) pregnant mice using wire myography. Maternal and fetal weights and pup-to-placenta ratio were not altered in ACE2KO at day 14 of gestation. However, the number of pups was reduced in ACE2KO [...

Hypertension, 2014

The balance between vasodilatory and vasoconstrictor prostanoids contributes to vascular control ... more The balance between vasodilatory and vasoconstrictor prostanoids contributes to vascular control during pregnancy. Alterations in this balance are involved in the development of hypertensive pregnancy. The transgenic female rat containing the human angiotensinogen (hAGN) gene mated with the male transgenic containing human renin (hREN) is a model of preeclampsia (TgA), and shows hypertension and proteinuria at late gestation. We investigated the role COX-derived mediators have on contractility of the uterine artery (UA) in TgA rats before the hypertensive phenotype develops. UA were isolated from transgenic TgA (n=9) and Sprague-Dawley (n=7) control rats at 7 days of gestation. UA were mounted in a wire myograph for determinations of isometric tension (DMT USA, 620M). Responses to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP) were measured in control conditions and after preincubation with indomethacin (Indo, 10-5M). Data were fitted to a dose response curv...

Hypertension, 2013

Endocannabinoids (ECs) are important contributors to implantation and decidualization and are sup... more Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamine (AEA), the endogenous ligand for the CB 1 and CB 2 receptor (R), interfere with receptivity of the blastocyst. Ang-(1-7) is present in the decidualized zones of the implantation site (IS) at early pregnancy and is down-regulated in the IS in normal pregnancy. We determined the effects of intra-uterine Ang-(1-7) on the EC system in the decidualized uterus. Ovariectomized rats were sensitized for the decidual cell reaction by steroid treatment. Decidualization was induced by infusion of phosphate buffered saline into the left horn (infused); the right horn was non-infused. Ang-(1-7) (24 μg/kg/hr) or vehicle was given into one of the two uterine horns. CB 1 R mRNA was reduced by decidualization but increased in the presence of Ang-(1-7) . CB 2 R mRNA was increased by decidualization and by Ang-(1-7) ( Figure). The enzyme metabolizing...

Circulation, 2020

Introduction: Recent evidences suggest that sex and estrogen can influence cerebrovascular reacti... more Introduction: Recent evidences suggest that sex and estrogen can influence cerebrovascular reactivity. We investigated the role of prostanoids and the estrogen receptor (ER) ex vivo in isolated middle cerebral arteries from male (M-MCA) and female (F-MCA) rats. Methods: MCA segments isolated from 20-week-old male and female Sprague-Dawley rats were mounted on a wire Multi Myograph (DMT) to measure isometric tone. Acetylcholine (ACh) was used to assess endothelium integrity. Concentration response curves to the thromboxane analog U46619 (U4, 10 -11 -10 -5 M) were performed in arteries intact or pre-treated with indomethacin (I,10 -5 M) or the ER antagonist G15 (G, 10 -6 M). Data were acquired with Powerlab 8 (ADInstruments) and recorded with LabChart v8 (ADInstruments). Response to K + was expressed in mN/mm whereas U4 maximal contraction as percent of maximal response to 75mM K + (%K MAX ) and sensitivity as pD 2 (-LogEC 50 ). Results: M-MCA (n=10) and F-MCA (n=13) displayed similar...

Hypertension, 2020

Men and women have different cardiovascular responses to spaceflight. We determined sex differenc... more Men and women have different cardiovascular responses to spaceflight. We determined sex differences in arterial stiffness, an independent risk factor for cardiovascular dysfunction, in rats after the exposure to 14-days of simulated weightlessness via hindlimb unloading (HLU). Male and female Sprague-Dawley rats at 20 weeks of age were either tail suspended via HLU or remained full-weight bearing in similar cages. Female control rats had lower body weight compared with males. There was no significant effect of HLU on body weight in either male or female rats. Our data demonstrate that HLU increased aortic pulse wave velocity, an index of arterial stiffness, in female rats (2.7 fold vs. control female- adjusted for body weight, n=5-6), but not in males. HLU had no effect on the levels of structural proteins (alpha smooth muscle actin or myosin) in either female or male rats. The levels of G-protein-coupled estrogen receptor 1 (GPER) were lower in the thoracic aorta of female rats exp...

Journal of Hypertension, 2021

Science of The Total Environment, 2017

The amount of ultraviolet (UV) radiation reaching the earth's surface has increas... more The amount of ultraviolet (UV) radiation reaching the earth's surface has increased due to ozone layer depletion, and this fact represents an opportunity to evaluate the physiological and behavioral responses of animals to this global-scale stressor. The transitory fish Girella laevifrons inhabits pools in the upper intertidal zone, which is characterized by exposure to a wide range of stressors, including UV radiation. We documented the field magnitude and the impact of UV radiation on oxygen consumption, body mass variations, and shelter (rocky and algae) selection by G. laevifrons. UV-exposed animals showed increased oxygen consumption, slower body weight increase, and active rocky shelter selection. Control fish showed increased body weight and no evident shelter selection. The results indicated that UV exposure affects fish energetic balance and habitat selection to favor greater protection against radiation. Increased UV exposure in transitory intertidal animals at levels observed in upper intertidal pools may alter the residency time of fish before leaving for the subtidal zone. Therefore, UV-induced energetic changes may determine animal performance and ontogenetic physiological itineraries, whereas shelter quality might determine habitat use.

Journal of Fish Biology, 2015

The effect of UV radiation on habitat use of two species of intertidal fishes that inhabit the sa... more The effect of UV radiation on habitat use of two species of intertidal fishes that inhabit the same pools but exhibit different activity levels and diets was measured: the highly active omnivorous Girella laevifrons and the cryptic carnivorous Graus nigra. Individuals of each species were acclimated to a tank divided in three sections with different illumination; no light (N/L), ultraviolet light (UV) and white light (WL), and the time spent and number of visits to each section were recorded. Although both species preferred the N/L section, G. laevifrons spent more time in UV and less time in WL compared with G. nigra; G. laevifrons also displayed higher number of visits to UV, suggesting a different tendency in space use in response to UV exposure in intertidal fishes.

Journal of the Marine Biological Association of the United Kingdom, 2012

Intertidal organisms have long been considered an ideal system to quantify how physical variation... more Intertidal organisms have long been considered an ideal system to quantify how physical variations determine differential energy allocations in specimens inhabiting environmental gradients such as exposure to wave action. In habitats with differential intertidal wave exposure (sheltered, Sh; and exposed, E) seasonal gonadal and foot weight variations and their associations with exposure and food availability (algae abundance) were determined in the keyhole limpetFissurella crassa. Gonadal weight is used as a measure of reproduction allocation whereas foot weight is an indirect indicator of energy allocation to survival. RNA:DNA ratio in limpets obtained from Sh and E habitats during the two different seasons was used as an indicator of biosynthetic capability. Our results indicate that algae abundance in E sites was higher in summer and lower in winter compared to Sh sites. In E sites the muscular foot weight of limpet was higher in summer in contrast to Sh sites whereF. crassamuscu...

Ocean & Coastal Management, 2014

Diversity and biological variability are key attributes to maintain a viable life system in the m... more Diversity and biological variability are key attributes to maintain a viable life system in the marine benthic zone and this balance is heavily affected by human activities. In Chile, Management and Exploitation Areas for Benthic Resources (MEABRs) are coastal areas administrated by local fishermen, which regulate the extraction of species of commercial of commercial importance (e.g. Concholepas concholepas, Fissurella spp. Loxechinus albus), key components of food webs. Both spatial and temporal impacts these species have on the structure and dynamics of the subtidal community are poorly understood. In one of the oldest MEABRs of Chile we evaluated spatial and temporal effects of controlled extraction of commercial species on subtidal macro invertebrate's diversity. Our results indicate that in a spatial scale MEABRs showed increased species richness, and important temporal changes in diversity and species composition from bivalves, ascidians and gastropods to cnidarians, sponges and bryozoans. We discuss possible mechanisms associated with the combined effects of fishery management and predation by key species on temporal composition variation in the subtidal macro invertebrate assemblage in this regulated area.

Marine and Freshwater Behaviour and Physiology, 2011

... J Shell Res , 23: 585–591. [Web of Science ®] View all references). Dahlhoff (200415. Clarke,... more ... J Shell Res , 23: 585–591. [Web of Science ®] View all references). Dahlhoff (200415. Clarke, A, Rodhouse, PG, Holmes, LJ and Pascoe, PL. 1989. Growth rate and nucleic acid ratio in cultured cuttlefish, Sepia officinalis (Mollusca: Cephalopda). ...

Journal of Cardiovascular Pharmacology, 2013

Ouabain-induced hypertension in rodents provides a model to study cardiovascular changes associat... more Ouabain-induced hypertension in rodents provides a model to study cardiovascular changes associated with human hypertension. We examined vascular function in rats after long-term treatment with ouabain. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in male Sprague-Dawley rats treated with ouabain (Oua, ~25 μg•day −1) or placebo for 8 weeks. Blood pressure increased in ouabain-treated animals, reaching 30% above baseline SBP after 7 weeks. At the end of treatment, vascular responses were studied in mesenteric resistance arteries (MRA) by wire myography. Contraction to potassium chloride (KCl) in intact and denuded arteries showed greater sensitivity in Oua-treated animals. Contraction to phenylephrine (PE) and relaxation to acetylcholine (ACh) were similar between groups with a lower response to sodium nitroprusside (SNP) in Oua-treated arteries. Sensitivity to endothelin-1 (ET-1) was higher in Ouatreated arteries. Na +-K + ATPase activity was decreased in MRA from Oua-treated animals, whereas protein expression of the Na +-K +-ATPase α 2 isoform was increased in heart and unchanged in mesenteric artery. Pre-incubation with indomethacin (10 −5 M) or L-NAME (10 −4 M) abolished the differences in KCl response and Na +-K + ATPase activity. Changes in MRA are consistent with enhanced vascular smooth muscle cell reactivity, a contributor to the increased vascular tone observed in this model of hypertension.

Chemistry

Molecular interactions of 4-diphenylmethoxy-1-methylpiperidine derivatives with the calcium chann... more Molecular interactions of 4-diphenylmethoxy-1-methylpiperidine derivatives with the calcium channel CaV1.1 (pdb:6JP5) are described. All the compounds tested, previously shown to inhibit adrenergic vascular contractions, display similar binding energetics and interactions with the trans-membrane domain of 6JP5 on the opposite side relative to the channel pore, where nifedipine, a known dihydropyridine Ca2+ channel blocker binds. Additionally, the compounds tested inhibit Ca2+-dependent contractions in isolated mouse mesenteric arteries. Thus, diphenylpyraline analogs may exert their anticontractile effects, at least partially, by blocking vascular Ca2+ channels.

Cells

The CB1 cannabinoid receptor (CB1R) and extracellular calcium (eCa2+)-stimulated Calcium Sensing ... more The CB1 cannabinoid receptor (CB1R) and extracellular calcium (eCa2+)-stimulated Calcium Sensing receptor (CaSR) can exert cellular signaling by modulating levels of intracellular calcium ([Ca2+]i). We investigated the mechanisms involved in the ([Ca2+]i) increase in N18TG2 neuroblastoma cells, which endogenously express both receptors. Changes in [Ca2+]i were measured in cells exposed to 0.25 or 2.5 mM eCa2+ by a ratiometric method (Fura-2 fluorescence) and expressed as the difference between baseline and peak responses (ΔF340/380). The increased ([Ca2+]i) in cells exposed to 2.5 mM eCa2+ was blocked by the CaSR antagonist, NPS2143, this inhibition was abrogated upon stimulation with WIN55212-2. WIN55212-2 increased [Ca2+]i at 0.25 and 2.5 mM eCa2+ by 700% and 350%, respectively, but this increase was not replicated by CP55940 or methyl-anandamide. The store-operated calcium entry (SOCE) blocker, MRS1845, attenuated the WIN55212-2-stimulated increase in [Ca2+]i at both levels of eC...

The FASEB Journal, 2012

ABSTRACT Both endothelin and the ET-1 receptor are altered in ouabain sensitive and hypertensive ... more ABSTRACT Both endothelin and the ET-1 receptor are altered in ouabain sensitive and hypertensive (mRen-2)27 transgenic rats, consistent with the lowering of blood pressure in both models of hypertension with either AT1 or ET-1 receptor blockade. We hypothesized that responses to ET-1 receptor activation are enhanced in the vasculature of the animals with acquired and genetic hypertension. Sprague-Dawley rats were implanted subcutaneously with a 60- day 1.5 mg ouabain (OUA) pellet (n = 6 control, n = 6 treated). Blood pressure (BP) was recorded daily via tail cuff for 8 weeks. Transgenic hypertensive (mRen-2)27 rats (n = 6) were also used. Third branch mesenteric arteries were mounted in a wire myograph (DMT-USA). Maximal responses to KCl and ET-1 were expressed as KMAX (mN/mm) and ET-1MAX (% KMAX) and sensitivity as pD2 (pD2=-Log[EC50]). Pre-incubation with indomethacin (10–5M) or LNAME (10–4M) were performed in parallel. OUA increased systolic BP by 30% (p<0.05) whereas age-matched (mRen-2)27 rats had a 55% higher BP vs control (p<0.05). ET-1MAX was similar in the three groups [ET-1MAX (mRen-2)27 136 ± 5%; OUA 128 ± 14% vs control 137 ± 8 % KMAX]. However sensitivity to ET-1 was increased in hypertensive vs control rat vasculature [(mRen-2)27 8.6 ± 0.1; OUA 8.5 ± 0.2 vs control 8 ± 0.1, p<0.05]. A greater sensitivity to ET-1 may serve as mediator of enhanced vascular tone in both models of hypertension.

Cannabis and cannabinoid research, Apr 3, 2023

Objectives: To investigate the role of COX-derived prostanoids and the endocannabinoids 2-arachid... more Objectives: To investigate the role of COX-derived prostanoids and the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) on uterine vascular control during early pregnancy in a rodent model of preeclampsia. Methods: The transgenic female rat containing the human angiotensinogen (hAGN) gene mated with the male transgenic containing human renin (hREN) is a model of preeclampsia (TgA). Uterine arteries (UA) were isolated from Sprague–Dawley (SD, n =7) and TgA (n = 9) rats at 7 days of gestation and mounted in a wire myograph (DMT-USA, 620 M). Concentration response curves were performed in control conditions and after preincubation with indomethacin (Indo, 10^-5M), or inhibitors of endocannabinoid hydrolysis: URB597 (FAAH) or JZL184 (MAGL) at 10^-6 M. Data were fitted to a dose response curve, maximal responses were expressed as percent of maximal response to 75mM KCl (% KMAX) and sensitivity as pD2 (pD2 =-Log[EC50]). Results: Responses to ACh reached similar maximal relaxations (64± 8 vs. 75± 6%, p \u3e0.05), an increased contraction in TgA UA at ACh \u3e10lM was eliminated by Indo. Contraction to Phe was similar in both groups with an inhibitory effect of Indo in TgA UA (p Conclusions: Blockade of COX enzymes inhibited ACh, Phe and Ang II contractions whereas endogenous AEA and 2-AG reduced TgA UA Ang II contraction. A pro-contractile role of COX-derived mediators and a counteracting role of AEA and 2-AG in the enhanced Ang II contraction in TgA UA are evident before the hypertensive phenotype is established. These interactions may control uterine vascular function in early stages of preeclampsia

Hypertension, 2014

Intrauterine fetal growth restriction (IUGR), one of the serious complications of pregnancy, incr... more Intrauterine fetal growth restriction (IUGR), one of the serious complications of pregnancy, increases the risk for perinatal morbidity and mortality, and cardiovascular and renal abnormalities later in life. The components of the renin-angiotensin system (RAS) are important mediators of uteroplacental vasculature during pregnancy. The distribution of angiotensin converting enzyme 2 (ACE2), a key enzyme of the RAS, is described in the invading and intravascular trophoblasts, decidual cells and in the umbilical cord. Deletion of ACE2 restricts fetal weight gain and reduces fetal-to-placental weights ratio. ACE2 deficiency results in augmented uterine artery contractility to Ang II at mid-gestation. In this study we determined whether uterine artery dysfunction is associated with placental abnormalities in ACE2 KO mice at mid-gestation. Systolic blood pressures were higher in pregnant ACE2 KO vs. C57BL/6 wild type (WT) (102.3±5.1 vs. 85.1±1.9 mmHg). Urinary protein excretion, serum cr...

Hypertension, 2014

Both the renin-angiotensin (RAS) and endocannabinoid (ECS) systems are down-regulated at the earl... more Both the renin-angiotensin (RAS) and endocannabinoid (ECS) systems are down-regulated at the early stages of normal pregnancy. The striking similarity of the pattern of distribution of the two systems and their required down-regulation in early events of pregnancy make a compelling argument to compare their regulation in the early events of pregnancy in an animal that has placental activation of the RAS at l ate gestation. Female transgenic rats with overexpression of human (h) angiotensinogen were mated with male rats with h renin [Preeclamptic model (PRE)]. At day 7 of gestation, normal pregnant Sprague Dawley (SD) and PRE animals were anesthetized and bovine serum albumin (BSA) conjugated to Alexa Fluor 488 was injected systemically to assess uterine permeability in the implantation (IS) and interimplantation (IIS) uterine sites. Mean blood pressures were not different between SD and PRE animals (98.8±2 vs 97±3 mmHg, p>0.05). Uterine permeability measured as the IS/IIS ratio o...

Hypertension, 2012

Fetal growth restriction (FGR) remains a leading cause of perinatal morbidity and mortality in hu... more Fetal growth restriction (FGR) remains a leading cause of perinatal morbidity and mortality in humans. Angiotensin converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system that influences the balance between angiotensin II (Ang II) and angiotensin-(1-7) (Ang-(1-7)). ACE2 is highly expressed in the human placenta and maternal stromal tissue in normal pregnancy; however its role in pregnancy is not well understood. Our previous studies revealed that pregnancy in ACE2-deficient mice (ACE2KO) is associated with restricted maternal and fetal weight, attenuated circulating Ang-(1-7), and increased placental Ang II at the end of pregnancy. Since the loss of ACE2 may lead to vascular dysfunction and FGR, we compared the uterine artery reactivity in ACE2KO versus wild-type C57Bl/6 (WT) pregnant mice using wire myography. Maternal and fetal weights and pup-to-placenta ratio were not altered in ACE2KO at day 14 of gestation. However, the number of pups was reduced in ACE2KO [...

Hypertension, 2014

The balance between vasodilatory and vasoconstrictor prostanoids contributes to vascular control ... more The balance between vasodilatory and vasoconstrictor prostanoids contributes to vascular control during pregnancy. Alterations in this balance are involved in the development of hypertensive pregnancy. The transgenic female rat containing the human angiotensinogen (hAGN) gene mated with the male transgenic containing human renin (hREN) is a model of preeclampsia (TgA), and shows hypertension and proteinuria at late gestation. We investigated the role COX-derived mediators have on contractility of the uterine artery (UA) in TgA rats before the hypertensive phenotype develops. UA were isolated from transgenic TgA (n=9) and Sprague-Dawley (n=7) control rats at 7 days of gestation. UA were mounted in a wire myograph for determinations of isometric tension (DMT USA, 620M). Responses to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP) were measured in control conditions and after preincubation with indomethacin (Indo, 10-5M). Data were fitted to a dose response curv...

Hypertension, 2013

Endocannabinoids (ECs) are important contributors to implantation and decidualization and are sup... more Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamine (AEA), the endogenous ligand for the CB 1 and CB 2 receptor (R), interfere with receptivity of the blastocyst. Ang-(1-7) is present in the decidualized zones of the implantation site (IS) at early pregnancy and is down-regulated in the IS in normal pregnancy. We determined the effects of intra-uterine Ang-(1-7) on the EC system in the decidualized uterus. Ovariectomized rats were sensitized for the decidual cell reaction by steroid treatment. Decidualization was induced by infusion of phosphate buffered saline into the left horn (infused); the right horn was non-infused. Ang-(1-7) (24 μg/kg/hr) or vehicle was given into one of the two uterine horns. CB 1 R mRNA was reduced by decidualization but increased in the presence of Ang-(1-7) . CB 2 R mRNA was increased by decidualization and by Ang-(1-7) ( Figure). The enzyme metabolizing...

Circulation, 2020

Introduction: Recent evidences suggest that sex and estrogen can influence cerebrovascular reacti... more Introduction: Recent evidences suggest that sex and estrogen can influence cerebrovascular reactivity. We investigated the role of prostanoids and the estrogen receptor (ER) ex vivo in isolated middle cerebral arteries from male (M-MCA) and female (F-MCA) rats. Methods: MCA segments isolated from 20-week-old male and female Sprague-Dawley rats were mounted on a wire Multi Myograph (DMT) to measure isometric tone. Acetylcholine (ACh) was used to assess endothelium integrity. Concentration response curves to the thromboxane analog U46619 (U4, 10 -11 -10 -5 M) were performed in arteries intact or pre-treated with indomethacin (I,10 -5 M) or the ER antagonist G15 (G, 10 -6 M). Data were acquired with Powerlab 8 (ADInstruments) and recorded with LabChart v8 (ADInstruments). Response to K + was expressed in mN/mm whereas U4 maximal contraction as percent of maximal response to 75mM K + (%K MAX ) and sensitivity as pD 2 (-LogEC 50 ). Results: M-MCA (n=10) and F-MCA (n=13) displayed similar...

Hypertension, 2020

Men and women have different cardiovascular responses to spaceflight. We determined sex differenc... more Men and women have different cardiovascular responses to spaceflight. We determined sex differences in arterial stiffness, an independent risk factor for cardiovascular dysfunction, in rats after the exposure to 14-days of simulated weightlessness via hindlimb unloading (HLU). Male and female Sprague-Dawley rats at 20 weeks of age were either tail suspended via HLU or remained full-weight bearing in similar cages. Female control rats had lower body weight compared with males. There was no significant effect of HLU on body weight in either male or female rats. Our data demonstrate that HLU increased aortic pulse wave velocity, an index of arterial stiffness, in female rats (2.7 fold vs. control female- adjusted for body weight, n=5-6), but not in males. HLU had no effect on the levels of structural proteins (alpha smooth muscle actin or myosin) in either female or male rats. The levels of G-protein-coupled estrogen receptor 1 (GPER) were lower in the thoracic aorta of female rats exp...

Journal of Hypertension, 2021

Science of The Total Environment, 2017

The amount of ultraviolet (UV) radiation reaching the earth's surface has increas... more The amount of ultraviolet (UV) radiation reaching the earth's surface has increased due to ozone layer depletion, and this fact represents an opportunity to evaluate the physiological and behavioral responses of animals to this global-scale stressor. The transitory fish Girella laevifrons inhabits pools in the upper intertidal zone, which is characterized by exposure to a wide range of stressors, including UV radiation. We documented the field magnitude and the impact of UV radiation on oxygen consumption, body mass variations, and shelter (rocky and algae) selection by G. laevifrons. UV-exposed animals showed increased oxygen consumption, slower body weight increase, and active rocky shelter selection. Control fish showed increased body weight and no evident shelter selection. The results indicated that UV exposure affects fish energetic balance and habitat selection to favor greater protection against radiation. Increased UV exposure in transitory intertidal animals at levels observed in upper intertidal pools may alter the residency time of fish before leaving for the subtidal zone. Therefore, UV-induced energetic changes may determine animal performance and ontogenetic physiological itineraries, whereas shelter quality might determine habitat use.

Journal of Fish Biology, 2015

The effect of UV radiation on habitat use of two species of intertidal fishes that inhabit the sa... more The effect of UV radiation on habitat use of two species of intertidal fishes that inhabit the same pools but exhibit different activity levels and diets was measured: the highly active omnivorous Girella laevifrons and the cryptic carnivorous Graus nigra. Individuals of each species were acclimated to a tank divided in three sections with different illumination; no light (N/L), ultraviolet light (UV) and white light (WL), and the time spent and number of visits to each section were recorded. Although both species preferred the N/L section, G. laevifrons spent more time in UV and less time in WL compared with G. nigra; G. laevifrons also displayed higher number of visits to UV, suggesting a different tendency in space use in response to UV exposure in intertidal fishes.

Journal of the Marine Biological Association of the United Kingdom, 2012

Intertidal organisms have long been considered an ideal system to quantify how physical variation... more Intertidal organisms have long been considered an ideal system to quantify how physical variations determine differential energy allocations in specimens inhabiting environmental gradients such as exposure to wave action. In habitats with differential intertidal wave exposure (sheltered, Sh; and exposed, E) seasonal gonadal and foot weight variations and their associations with exposure and food availability (algae abundance) were determined in the keyhole limpetFissurella crassa. Gonadal weight is used as a measure of reproduction allocation whereas foot weight is an indirect indicator of energy allocation to survival. RNA:DNA ratio in limpets obtained from Sh and E habitats during the two different seasons was used as an indicator of biosynthetic capability. Our results indicate that algae abundance in E sites was higher in summer and lower in winter compared to Sh sites. In E sites the muscular foot weight of limpet was higher in summer in contrast to Sh sites whereF. crassamuscu...

Ocean & Coastal Management, 2014

Diversity and biological variability are key attributes to maintain a viable life system in the m... more Diversity and biological variability are key attributes to maintain a viable life system in the marine benthic zone and this balance is heavily affected by human activities. In Chile, Management and Exploitation Areas for Benthic Resources (MEABRs) are coastal areas administrated by local fishermen, which regulate the extraction of species of commercial of commercial importance (e.g. Concholepas concholepas, Fissurella spp. Loxechinus albus), key components of food webs. Both spatial and temporal impacts these species have on the structure and dynamics of the subtidal community are poorly understood. In one of the oldest MEABRs of Chile we evaluated spatial and temporal effects of controlled extraction of commercial species on subtidal macro invertebrate's diversity. Our results indicate that in a spatial scale MEABRs showed increased species richness, and important temporal changes in diversity and species composition from bivalves, ascidians and gastropods to cnidarians, sponges and bryozoans. We discuss possible mechanisms associated with the combined effects of fishery management and predation by key species on temporal composition variation in the subtidal macro invertebrate assemblage in this regulated area.

Marine and Freshwater Behaviour and Physiology, 2011

... J Shell Res , 23: 585–591. [Web of Science ®] View all references). Dahlhoff (200415. Clarke,... more ... J Shell Res , 23: 585–591. [Web of Science ®] View all references). Dahlhoff (200415. Clarke, A, Rodhouse, PG, Holmes, LJ and Pascoe, PL. 1989. Growth rate and nucleic acid ratio in cultured cuttlefish, Sepia officinalis (Mollusca: Cephalopda). ...

Journal of Cardiovascular Pharmacology, 2013

Ouabain-induced hypertension in rodents provides a model to study cardiovascular changes associat... more Ouabain-induced hypertension in rodents provides a model to study cardiovascular changes associated with human hypertension. We examined vascular function in rats after long-term treatment with ouabain. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in male Sprague-Dawley rats treated with ouabain (Oua, ~25 μg•day −1) or placebo for 8 weeks. Blood pressure increased in ouabain-treated animals, reaching 30% above baseline SBP after 7 weeks. At the end of treatment, vascular responses were studied in mesenteric resistance arteries (MRA) by wire myography. Contraction to potassium chloride (KCl) in intact and denuded arteries showed greater sensitivity in Oua-treated animals. Contraction to phenylephrine (PE) and relaxation to acetylcholine (ACh) were similar between groups with a lower response to sodium nitroprusside (SNP) in Oua-treated arteries. Sensitivity to endothelin-1 (ET-1) was higher in Ouatreated arteries. Na +-K + ATPase activity was decreased in MRA from Oua-treated animals, whereas protein expression of the Na +-K +-ATPase α 2 isoform was increased in heart and unchanged in mesenteric artery. Pre-incubation with indomethacin (10 −5 M) or L-NAME (10 −4 M) abolished the differences in KCl response and Na +-K + ATPase activity. Changes in MRA are consistent with enhanced vascular smooth muscle cell reactivity, a contributor to the increased vascular tone observed in this model of hypertension.

Chemistry

Molecular interactions of 4-diphenylmethoxy-1-methylpiperidine derivatives with the calcium chann... more Molecular interactions of 4-diphenylmethoxy-1-methylpiperidine derivatives with the calcium channel CaV1.1 (pdb:6JP5) are described. All the compounds tested, previously shown to inhibit adrenergic vascular contractions, display similar binding energetics and interactions with the trans-membrane domain of 6JP5 on the opposite side relative to the channel pore, where nifedipine, a known dihydropyridine Ca2+ channel blocker binds. Additionally, the compounds tested inhibit Ca2+-dependent contractions in isolated mouse mesenteric arteries. Thus, diphenylpyraline analogs may exert their anticontractile effects, at least partially, by blocking vascular Ca2+ channels.

Cells

The CB1 cannabinoid receptor (CB1R) and extracellular calcium (eCa2+)-stimulated Calcium Sensing ... more The CB1 cannabinoid receptor (CB1R) and extracellular calcium (eCa2+)-stimulated Calcium Sensing receptor (CaSR) can exert cellular signaling by modulating levels of intracellular calcium ([Ca2+]i). We investigated the mechanisms involved in the ([Ca2+]i) increase in N18TG2 neuroblastoma cells, which endogenously express both receptors. Changes in [Ca2+]i were measured in cells exposed to 0.25 or 2.5 mM eCa2+ by a ratiometric method (Fura-2 fluorescence) and expressed as the difference between baseline and peak responses (ΔF340/380). The increased ([Ca2+]i) in cells exposed to 2.5 mM eCa2+ was blocked by the CaSR antagonist, NPS2143, this inhibition was abrogated upon stimulation with WIN55212-2. WIN55212-2 increased [Ca2+]i at 0.25 and 2.5 mM eCa2+ by 700% and 350%, respectively, but this increase was not replicated by CP55940 or methyl-anandamide. The store-operated calcium entry (SOCE) blocker, MRS1845, attenuated the WIN55212-2-stimulated increase in [Ca2+]i at both levels of eC...

The FASEB Journal, 2012

ABSTRACT Both endothelin and the ET-1 receptor are altered in ouabain sensitive and hypertensive ... more ABSTRACT Both endothelin and the ET-1 receptor are altered in ouabain sensitive and hypertensive (mRen-2)27 transgenic rats, consistent with the lowering of blood pressure in both models of hypertension with either AT1 or ET-1 receptor blockade. We hypothesized that responses to ET-1 receptor activation are enhanced in the vasculature of the animals with acquired and genetic hypertension. Sprague-Dawley rats were implanted subcutaneously with a 60- day 1.5 mg ouabain (OUA) pellet (n = 6 control, n = 6 treated). Blood pressure (BP) was recorded daily via tail cuff for 8 weeks. Transgenic hypertensive (mRen-2)27 rats (n = 6) were also used. Third branch mesenteric arteries were mounted in a wire myograph (DMT-USA). Maximal responses to KCl and ET-1 were expressed as KMAX (mN/mm) and ET-1MAX (% KMAX) and sensitivity as pD2 (pD2=-Log[EC50]). Pre-incubation with indomethacin (10–5M) or LNAME (10–4M) were performed in parallel. OUA increased systolic BP by 30% (p<0.05) whereas age-matched (mRen-2)27 rats had a 55% higher BP vs control (p<0.05). ET-1MAX was similar in the three groups [ET-1MAX (mRen-2)27 136 ± 5%; OUA 128 ± 14% vs control 137 ± 8 % KMAX]. However sensitivity to ET-1 was increased in hypertensive vs control rat vasculature [(mRen-2)27 8.6 ± 0.1; OUA 8.5 ± 0.2 vs control 8 ± 0.1, p<0.05]. A greater sensitivity to ET-1 may serve as mediator of enhanced vascular tone in both models of hypertension.