L-serine, a non-essential amino acid, plays a role in the biosynthesis of the amino acids, proteins, purine and pyrimidine nucleotides. It is important for the proper functioning of the nervous system. It has been considered in the treatment of patients with schizophrenia, depression, chronic fatigue syndrome and psychomotor retardation, and of the seizures encountered in patients with rare inborn errors of L-serine biosynthesis. However, there are no reports in the literature of the direct cardiovascular effects of L-serine. Using normotensive Sprague-Dawley rats, Sprague-Dawley rats rendered hypertensive by chronic treatment with the nitric oxide (NO) synthase inhibitior NG nitro L-arginine methyl ester (L-NAME) and spontaneously hypertensive rats (SHR), the present study examined the in vitro and in vivo effects of L-serine. In vitro studies focused on L-serine induced changes in phenylephrine constricted third order branches of rat mesenteric arterioles while the in vivo studies examined the effects of intravenous infusion of L-serine on mean arterial pressure (MAP) and heart rate (HR) in intact anaesthetized rats. L-serine (10 to 200 µmol/L) evoked concentration-dependent vasodilatation in phenylephrine constricted endothelium-intact, but not in endothelium-denuded, rat mesenteric arterioles. The vasodilator responses to L-serine were absent in the combined presence of apamin, a calcium activated small conductance potassium (SKCa) channel inhibitor, and TRAM-34, a calcium activated intermediate conductance potassium (IKCa) channel inhibitor, or ouabain, a sodium pump inhibitor and barium (Ba2+), an inward rectifying potassium (Kir) channel inhibitor, or when the vessels were depolarized by potassium chloride. The maximal vasodilatation response (Emax) to L-serine was higher in vessels from L-NAME treated rats (40%) than from control rats (20%). In anesthetized rats, L-serine evoked a rapid, reversible, dose-dependent fall in MAP (without a significant change in HR), which was more pronounced in L-NAME treated rats (> 60 mmHg) than in normotensive control rats (25 mmHg). The fall in MAP was inhibited (p<0.01) by apamin plus charybdotoxin pretreatment. Charybdotoxin was used in place of Tram-34 in in vivo studies since Tram-34 is not soluble in water or saline. In age matched Sprague-Dawley, Wistar-Kyoto (WKY) and SHR strains, D-serine had the same effects on MAP and HR as L-serine; however, L-serine evoked a greater maximal fall in MAP in all strains, and the effect was more pronounced in hypertensive rats. In contrast, the infusion of glycine, a metabolite of L-serine led to a dose-dependent fall in MAP in normotensive rats but a dose-dependent increase in MAP in both SHR and L-NAME treated hypertensive WKY rats. Both the depressor and pressor responses to glycine were abolished by pretreatment with the N-methyl D-aspartate receptor antagonist, MK-801. Regional hemodynamic studies performed using the fluorescent tagged microsphere distribution technique revealed that the fall in MAP and profound decrease in total peripheral resistance (TPR) evoked by acute L-serine infusion is due to increased blood flow in the splanchnic region and more particularly in the small intestinal vascular beds. This effect is blocked by the combined treatment with the KCa channel inhibitors, apamin plus charybdotoxin. Although resting MAP and TPR are higher, and cardiac output (CO) is lower both in SHR and in WKY rats rendered hypertensive by L-NAME treatment compared to normotensive WKY rats, L-serine infusion leads to a rapid fall in TPR and MAP, and an increase in CO in all models. This effect was more profound in the hypertensive rats. These findings suggest that L-serine could be helpful in overcoming splanchnic organ failure observed in patients with cardiopulmonary bypass. In addition, L-serine, either alone or in combination with other antihypertensive medications, could be considered in the management of endothelial dysfunctional states with reduced NO bioavailability such as hypertension and diabetes.

L-serine, a non-essential amino acid, plays a role in the biosynthesis of the amino acids, proteins, purine and pyrimidine nucleotides. It is important for the proper functioning of the nervous system. It has been considered in the treatment of patients with schizophrenia, depression, chronic fatigue syndrome and psychomotor retardation, and of the seizures encountered in patients with rare inborn errors of L-serine biosynthesis. However, there are no reports in the literature of the direct cardiovascular effects of L-serine. Using normotensive Sprague-Dawley rats, Sprague-Dawley rats rendered hypertensive by chronic treatment with the nitric oxide (NO) synthase inhibitior NG nitro L-arginine methyl ester (L-NAME) and spontaneously hypertensive rats (SHR), the present study examined the in vitro and in vivo effects of L-serine. In vitro studies focused on L-serine induced changes in phenylephrine constricted third order branches of rat mesenteric arterioles while the in vivo studies examined the effects of intravenous infusion of L-serine on mean arterial pressure (MAP) and heart rate (HR) in intact anaesthetized rats. L-serine (10 to 200 µmol/L) evoked concentration-dependent vasodilatation in phenylephrine constricted endothelium-intact, but not in endothelium-denuded, rat mesenteric arterioles. The vasodilator responses to L-serine were absent in the combined presence of apamin, a calcium activated small conductance potassium (SKCa) channel inhibitor, and TRAM-34, a calcium activated intermediate conductance potassium (IKCa) channel inhibitor, or ouabain, a sodium pump inhibitor and barium (Ba2+), an inward rectifying potassium (Kir) channel inhibitor, or when the vessels were depolarized by potassium chloride. The maximal vasodilatation response (Emax) to L-serine was higher in vessels from L-NAME treated rats (40%) than from control rats (20%). In anesthetized rats, L-serine evoked a rapid, reversible, dose-dependent fall in MAP (without a significant change in HR), which was more pronounced in L-NAME treated rats (> 60 mmHg) than in normotensive control rats (25 mmHg). The fall in MAP was inhibited (p<0.01) by apamin plus charybdotoxin pretreatment. Charybdotoxin was used in place of Tram-34 in in vivo studies since Tram-34 is not soluble in water or saline. In age matched Sprague-Dawley, Wistar-Kyoto (WKY) and SHR strains, D-serine had the same effects on MAP and HR as L-serine; however, L-serine evoked a greater maximal fall in MAP in all strains, and the effect was more pronounced in hypertensive rats. In contrast, the infusion of glycine, a metabolite of L-serine led to a dose-dependent fall in MAP in normotensive rats but a dose-dependent increase in MAP in both SHR and L-NAME treated hypertensive WKY rats. Both the depressor and pressor responses to glycine were abolished by pretreatment with the N-methyl D-aspartate receptor antagonist, MK-801. Regional hemodynamic studies performed using the fluorescent tagged microsphere distribution technique revealed that the fall in MAP and profound decrease in total peripheral resistance (TPR) evoked by acute L-serine infusion is due to increased blood flow in the splanchnic region and more particularly in the small intestinal vascular beds. This effect is blocked by the combined treatment with the KCa channel inhibitors, apamin plus charybdotoxin. Although resting MAP and TPR are higher, and cardiac output (CO) is lower both in SHR and in WKY rats rendered hypertensive by L-NAME treatment compared to normotensive WKY rats, L-serine infusion leads to a rapid fall in TPR and MAP, and an increase in CO in all models. This effect was more profound in the hypertensive rats. These findings suggest that L-serine could be helpful in overcoming splanchnic organ failure observed in patients with cardiopulmonary bypass. In addition, L-serine, either alone or in combination with other antihypertensive medications, could be considered in the management of endothelial dysfunctional states with reduced NO bioavailability such as hypertension and diabetes.

Sepsis, a great challenge to the physician, is characterized with massive oxidative stress of tissue, cytokine inflammation and increases in nitric oxide (NO) production. Meanwhile, free radical induced by oxidative stress also injures cell membrane or DNA. The way to terminate free radical chain reaction is to administer antioxidant. The commonly used anesthetic, propofol, was thought to be with antioxidant capacity. In the first part of this thesis, we investigated the different role of oxidative injury and NO via systemic injection of LPS in rats. We demonstrated oxidative injury is associated with both early and late stage whereas NO is engaged primarily in late stage cardiovascular depression. Propofol, a rapid onset and fast recovery anesthetic, is attributed to protect anainst cardiovascular depression via attenuating the late stage NO surge in aorta by inhibition of iNOS upregulation. We also examine the influence of propofol on temporal changes in power density of frequency components of systemic arterial pressure (SAP) variability in rat with sepsis and the role of inducible NO synthase (iNOS). We have the conclusions that iNOS-induced NO might be involved in the manifestation of high-frequency and low-frequency components of the SAP spectrum during endotoxemia when low-dose propofol is used and the effect of NO is blunted when high-dose propofol is administered. Due to further investigation was needed to the cellular protective mechanisms of propofol, we delineate the effect of propofol to free radical related enzymel involved in sepsis via both in vivo and vitro studies with rats subjected to LPS (15 mg/kg) and H9C2, L2, NR8383 (derived from rat cardiac myocyte, lung, macrophage, respectively), respectively. Our results demonstrated that propofol may play the major protective role on iNOS, superoxide dismutase and p47 phox oxidative enzymes on lung epithelial cells. Propofol also provided protective effects on cardiac myocyte and macrophage with suppression of iNOS only although free radical production were all significantly suppressed. Ischemia-reperfusion (IR) injury may also produce a lot of free radical and cytokines to cause tissue damage and is common in clinical. We investigated the effect of propofol on free radical and cytokine production via this different model and compared with another rapid recovery anesthesitc, sevoflurane. Aortic decalmping surgery in porcine and their monocyte, aortic and coronary smooth muscle cells were applied for in vivo and in vitro model, respectively. We also demonstrated that propofol but not sevoflurane suppressed the production of free radical and cytokine in monocyte and smooth muscle cells but not in vivo model. In sepsis and IR model that produced a lot free radical and cytokines, propofol eliminated the free redical and cytokines via suppressed different kinds of oxidative enzymes in different cells of different organs to express its protective role. However, as an anesthetic, propofol must be used carefully to perform its maximal benefit.

This thesis presents an investigation of statistical analytical methods applied to the analysis of the shape of the arterial pressure waveform. The arterial pulse is analysed by a selection of both supervised and unsupervised methods of learning. Supervised learning methods are generally better known as regression. Unsupervised learning methods seek patterns in data without the specification of a target variable. The theoretical relationship between arterial pressure and wave shape is first investigated by study of a transmission line model of the arterial tree. A meta-database of pulse waveforms obtained by the SphygmoCor"??" device is then analysed by the unsupervised learning technique of Self Organising Maps (SOM). The map patterns indicate that the observed arterial pressures affect the wave shape in a similar way as predicted by the theoretical model. A database of continuous arterial pressure obtained by catheter line during sleep is used to derive supervised models that enable estimation of arterial pressures, based on the measured wave shapes. Independent component analysis (ICA) is also used in a supervised learning methodology to show the theoretical plausibility of separating the pressure signals from unwanted noise components. The accuracy and repeatability of the SphygmoCor?? device is measured and discussed. Alternative regression models are introduced that improve on the existing models in the estimation of central cardiovascular parameters from peripheral arterial wave shapes. Results of this investigation show that from the information in the wave shape, it is possible, in theory, to estimate the continuous underlying pressures within the artery to a degree of accuracy acceptable to the Association for the Advancement of Medical Instrumentation. This could facilitate a new role for non-invasive sphygmographic devices, to be used not only for feature estimation but as alternatives to invasive arterial pressure sensors in the measurement of continuous blood pressure.

This thesis presents four studies investigating the phenomenon of post exercise hypotension in the human condition of pre (borderline)-hypertension. Study one investigated the effects of an acute bout of 30-minutes upright cycling on post exercise haemodynamics and compared the results to a non-exercise control condition. 9 pre-hypertensive males, mean arterial pressure (MAP) = 106 ± 5 mmHg (50 ± 10 yr), not on medication, were studied for 6 hours following 30-minutes of cycle exercise at 70% maximal oxygen consumption and following 30-minutes of seated rest. Results demonstrate that moderate intensity exercise exerts a modest fall (~6 mmHg) in arterial pressure with the hypotension sustained for 6-hours post exercise. The fall in arterial pressure equates to a significantly reduced after load when compared to both pre-exercise baseline and non-exercise control data taken at the same time of day. The arterial pressure responses transcended into a sustained reduction (20%) in systemic vascular resistance and reciprocal increase in vascular conductance for up to 2-hours post-exercise. Venous atrial natriuretic peptide (ANP) demonstrated an elevation (44%) following exercise and a significant decline (33%) in the post-exercise period mirroring the haemodynamic response. This research reveals that acute exercise is capable of sustained reductions in arterial pressure and vascular resistance beyond the usual labile fluctuations and that the octapeptide ANP may exert a modulatory influence over the post-exercise response. Increases in 02 tension beyond the physiological range induces complex effects on the circulatory system with a dominant vasoconstriction following hyperoxia. The purpose of study 2 was to assess the effects of hypoxic (16% 02) and hyperoxic (50% 62) exercise on subsequent haemodynamic control when compared with normoxia. 9 pre-hypertensive males, MAP = 106 ± 5 mmHg (50 ±10 yr), not on medication, performed 30-minutes of cycle exercise at 70% normoxic maximal oxygen consumption in hypoxia (16% O 2 ), hyperoxia (50% O 2) and normoxia(21% O2 ). Hyperoxic exercise blunted post-exercise haemodynamics by significantly attenuating the reductions (from normoxic baseline) in SVR (-45%, PO.05 vs. normoxic & hypoxic exercise immediately post-exercise) that persisted throughout 120-minutes recovery in normoxia (-35% vs. normoxic & hypoxic exercise, during recovery) and elicited a mildly hypertensive effect, with regards to MAP, whereas normoxic and hypoxic exercise elicited a hypotension compared to baseline (P < 0.05). Circulating ANP was decreased in the hyperoxic trial when compared with normoxic and hypoxic exercise [24.3 (13.4) v. 31.5 (16.3) and 29.6 (13.9) pg/ml, respectively; P < 0.05, pooled for state]. Changes in MAP were related to changes in ANP concentration only following hyperoxic exercise (r = 0.50, P < 0.01). These findings indicate that acute modest hyperoxia reflexively induces measurable physiological derangement partly explained by decreased circulating concentrations of ANP. Study three determined the role of free-radical mediated oxidative stress and redox regulation of circulating NO metabolism as a primary modulator of vascular tone following exercise in pre-hypertensive humans. Utilising the same cohort and exercise protocol as in study 1 venous blood was sampled from an antecubital vein. Plasma NO metabolites nitrate (NO" 3 ) and nitrite (NO"2 ) were determined fluorometrically, whilst S-Nitrosothiol (RSNO) concentrations were assayed by the Saville reaction Indirect markers of oxidative stress were determined spectrophotometrically detecting lipid hydroperoxides (LOOH). Exercise led to a delayed increase in LOOH by 60- minutes post-exercise (0.69 ± 0.13 v. 0.86 ± 0.18 umol/1, respectively, P < 0.05), that remained elevated until termination of the trial 6-hours post-exercise. NO'a significantly fell below baseline by 120-minutes post-exercise (10.8 ± 3.3 v. 1.1 ±1.1 u.mol/1, respectively, P < 0.05), remaining attenuated for the remainder of the study.NO'i and RSNO were unmodified in the post-exercise period. In parallel to this finding the data also indicates a significant blunting in the hyperaemic response [SVR decreased from a 31% reduction immediately (within 1-minute) post-exercise to -13 and 8% at 60- and 120-minutes post-exercise, respectively, P < 0.05] and reversal of the hypotension (P < 0.05) over the same time frame as the augmented lipid peroxidation and attenuated circulating NO~3. These results indicate that augmented oxidative stress exerts a deleterious effect on post-exercise haemodynamics and implicates a potential redox regulation pathway of NO as being a mechanism by which free radical-induced oxidative stress blunts the degree of PEH in the recovery period. The final study investigated the potential role of a redox-mediated regulation of circulating NO bioavailability as a modulator of the augmented vasoconstriction following hyperoxic exercise. The same cohort and exercise protocol were employed as in study 2 and venous blood was assayed for NO"3 , NO'a, RSNO, LOOK, & lipid /water-soluble antioxidant concentrations. Similar adverse haemodynamic effects were noted following hyperoxic exercise as reported previously in study 2. RSNO showed a significant increase following hypoxic exercise only (P < Q.Q5, state x time, interaction), whereas NO~3, NO~2 and LOOH failed to differ between conditions (P > 0.05, main effect for state [02] and state x time, interaction effects). Ascorbic acid was mobilised in response to hyperoxic exercise when compared to normoxia (P < 0.05, main effect for state [O2] and state x time, interaction effects) being significantly elevated by 120-minutes post-exercise in hyperoxia compared to normoxia and hypoxia [75.1 (31) v. 39.5 (18.3) v. 46.7 (14.2) |amol/l, respectively, P < 0.05]. This data demonstrates an effective endogenous antioxidant response and argues against a redox regulation pathway of NO metabolism as a primary mediator of blunted vasodilatation in this scenario. This elucidates a more complex regulation of arterial tone, resulting from a metabolic pathway independent of NO in older subjects with pre-hypertension. This work demonstrates that (1) aerobic exercise exerts a hypotensive effect in humans with pre-hypertension, (2) ANP plays a part in the vasodilatation following exercise, (3) Free-radical mediated oxidative stress & subsequent modulation of NO metabolism exerts a deleterious influence on post-exercise haemodynamics (4) Acute hyperoxic exercise induces a sustained vasoconstriction that is mediated via circulating ANP concentration but not by redox regulation of NO metabolism.

Made available in DSpace on 2015-06-17T19:33:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-03-26. Added 1 bitstream(s) on 2015-06-18T12:47:54Z : No. of bitstreams: 1 000827092_20160326.pdf: 264009 bytes, checksum: 2d4bf1818fcf3504d633d098c466fc39 (MD5) Bitstreams deleted on 2016-03-28T13:37:47Z: 000827092_20160326.pdf,. Added 1 bitstream(s) on 2016-03-28T13:38:49Z : No. of bitstreams: 1 000827092.pdf: 684285 bytes, checksum: eba84188e19e273d98a9610df1d7fb48 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução: embora a literatura relate alterações cardiovasculares induzidas pela exposição ao etanol e ao chumbo (Pb) isoladamente na vida adulta, há escassez de estudos focando os efeitos cardiovasculares pós-natal da exposição ao etanol e/ou Pb in utero. Objetivos: investigar possíveis alterações nas respostas cardiovasculares de ratos recém-desmamados expostos pré-natalmente ao etanol e ao Pb, isoladamente e em associação. Ainda, avançar na compreensão dos mecanismos envolvidos nestas alterações. Materiais e Métodos: foram utilizados ratos machos Wistar recém-desmamados (25-28 dias de idade) provenientes de mães dos grupos: controle - recebeu água de beber ad libitum; Pb - recebeu chumbo 500 ppm ad libitum durante a prenhez; EtOH - recebeu solução de etanol a 10% na água de beber ad libitum durante a prenhez; e Pb/EtOH - ambos protocolos em associação. Esses animais foram mortos e anéis de aorta torácica foram coletados e mantidos em banho isolado contendo solução de Krebs-Henseleit, 37ºC, pH 7.4, saturado com 95% de O2 e 5% CO2. Curvas concentração-efeito ao L-NAME, à acetilcolina (ACh), na ausência e presença de indometacina e/ou L-NAME, e ao nitroprussiato de sódio foram obtidas de anéis de aorta intacta e desnuda. Avaliou-se ainda a pressão arterial no 25º dia de vida pós-natal. Concentração eficaz 50% (CE50) e resposta máxima (RM) foram avaliadas (MANOVA/Tukey). Resultados: a associação da exposição ao Pb e ao etanol in utero, mas não os protocolos isolados, determinou hipertensão arterial no 25º dia de vida pós-natal (sistólica - controle 135,5 ± 3,0, Pb/EtOH 157,8 ± 4,6*; diastólica - controle 97,5 ± 1,4, Pb/EtOH 125,9 ± 3,2*; *P < 0,05, n=11). Nenhum dos protocolos determinou qualquer alteração da reatividade da aorta intacta e desnuda ao L-NAME e ao nitroprussiato de sódio (RM e CE50) e de CE50 à ACh em aorta intacta (dados não mostrados). Entretanto, a ... / Introduction: although the literature reports cardiovascular changes induced by exposure to ethanol and lead (Pb) alone in adulthood, few studies focus on postnatal cardiovascular effects of exposure to ethanol and/or Pb in utero. Objectives: it was to investigate possible changes in the cardiovascular responses of weaned rats prenatally exposed to ethanol and Pb, alone and in combination. Still, advancing our understanding of the mechanisms involved in these changes. Materials and Methods: mothers were separated in 4 groups: control - received drinking water ad libitum ; Pb - received lead 500 ppm ad libitum during pregnancy ; EtOH - received a solution of 10% ethanol ad libitum in drinking water during pregnancy , and Pb / EtOH - both protocols in combination. Male Wistar rats (25 to 28-day old) from exposed mothers were used. The animals were sacrificed and thoracic aortic rings were collected and kept in organ bath containing Krebs- Henseleit solution, 37°C, pH 7.4, saturated with 95% O2 and 5% CO2. Concentration-effect curves to L-NAME, acetylcholine (ACh) in absence and presence of indomethacin and/or L-NAME, and sodium nitroprusside were obtained in intact and/or denuded aortas. It was also evaluated the blood pressure of 25-day old rats from all groups. Effective concentration 50% (EC50) and maximum response (MR) were evaluated (MANOVA/Tukey). Results: association of Pb exposure and ethanol in utero, but not the isolated protocols, determined hypertension on the 25th day of postnatal life (systolic - control 135.5 ± 3.0, Pb/EtOH 157.8 ± 4.6*; diastolic - control 97.5 ± 1.4, Pb/EtOH 125.9 ± 3.2*, *P < 0.05, n=11). None of the protocols determined any change in reactivity of intact and denuded aortas to L-NAME and sodium nitroprusside (MR and EC50) and EC50 to ACh in intact aortas (data not shown). Removal of endothelium abolished vasorelaxation to ACh. Unlike in utero exposure to Pb ...

Orientador: Sandra Cordellini / Banca: Carlos Alan Cândido Dias Junior / Banca: Andréia Fresneda Gaspar / Resumo: Introdução: embora a literatura relate alterações cardiovasculares induzidas pela exposição ao etanol e ao chumbo (Pb) isoladamente na vida adulta, há escassez de estudos focando os efeitos cardiovasculares pós-natal da exposição ao etanol e/ou Pb in utero. Objetivos: investigar possíveis alterações nas respostas cardiovasculares de ratos recém-desmamados expostos pré-natalmente ao etanol e ao Pb, isoladamente e em associação. Ainda, avançar na compreensão dos mecanismos envolvidos nestas alterações. Materiais e Métodos: foram utilizados ratos machos Wistar recém-desmamados (25-28 dias de idade) provenientes de mães dos grupos: controle - recebeu água de beber ad libitum; Pb - recebeu chumbo 500 ppm ad libitum durante a prenhez; EtOH - recebeu solução de etanol a 10% na água de beber ad libitum durante a prenhez; e Pb/EtOH - ambos protocolos em associação. Esses animais foram mortos e anéis de aorta torácica foram coletados e mantidos em banho isolado contendo solução de Krebs-Henseleit, 37ºC, pH 7.4, saturado com 95% de O2 e 5% CO2. Curvas concentração-efeito ao L-NAME, à acetilcolina (ACh), na ausência e presença de indometacina e/ou L-NAME, e ao nitroprussiato de sódio foram obtidas de anéis de aorta intacta e desnuda. Avaliou-se ainda a pressão arterial no 25º dia de vida pós-natal. Concentração eficaz 50% (CE50) e resposta máxima (RM) foram avaliadas (MANOVA/Tukey). Resultados: a associação da exposição ao Pb e ao etanol in utero, mas não os protocolos isolados, determinou hipertensão arterial no 25º dia de vida pós-natal (sistólica - controle 135,5 ± 3,0, Pb/EtOH 157,8 ± 4,6*; diastólica - controle 97,5 ± 1,4, Pb/EtOH 125,9 ± 3,2*; *P < 0,05, n=11). Nenhum dos protocolos determinou qualquer alteração da reatividade da aorta intacta e desnuda ao L-NAME e ao nitroprussiato de sódio (RM e CE50) e de CE50 à ACh em aorta intacta (dados não mostrados). Entretanto, a ... / Abstract: Introduction: although the literature reports cardiovascular changes induced by exposure to ethanol and lead (Pb) alone in adulthood, few studies focus on postnatal cardiovascular effects of exposure to ethanol and/or Pb in utero. Objectives: it was to investigate possible changes in the cardiovascular responses of weaned rats prenatally exposed to ethanol and Pb, alone and in combination. Still, advancing our understanding of the mechanisms involved in these changes. Materials and Methods: mothers were separated in 4 groups: control - received drinking water ad libitum ; Pb - received lead 500 ppm ad libitum during pregnancy ; EtOH - received a solution of 10% ethanol ad libitum in drinking water during pregnancy , and Pb / EtOH - both protocols in combination. Male Wistar rats (25 to 28-day old) from exposed mothers were used. The animals were sacrificed and thoracic aortic rings were collected and kept in organ bath containing Krebs- Henseleit solution, 37°C, pH 7.4, saturated with 95% O2 and 5% CO2. Concentration-effect curves to L-NAME, acetylcholine (ACh) in absence and presence of indomethacin and/or L-NAME, and sodium nitroprusside were obtained in intact and/or denuded aortas. It was also evaluated the blood pressure of 25-day old rats from all groups. Effective concentration 50% (EC50) and maximum response (MR) were evaluated (MANOVA/Tukey). Results: association of Pb exposure and ethanol in utero, but not the isolated protocols, determined hypertension on the 25th day of postnatal life (systolic - control 135.5 ± 3.0, Pb/EtOH 157.8 ± 4.6*; diastolic - control 97.5 ± 1.4, Pb/EtOH 125.9 ± 3.2*, *P < 0.05, n=11). None of the protocols determined any change in reactivity of intact and denuded aortas to L-NAME and sodium nitroprusside (MR and EC50) and EC50 to ACh in intact aortas (data not shown). Removal of endothelium abolished vasorelaxation to ACh. Unlike in utero exposure to Pb ... / Mestre

O estresse é entendido como o produto da relação do homem com o meio ambiente. Um evento estressor pode desencadear um conjunto de reações fisiológicas capazes de levar ao desequilíbrio do organismo. Os serviços de saúde proporcionam condições de trabalho reconhecidamente tensiógenas. O trabalho da equipe de enfermagem em Centro de Terapia Intensiva se revela potencialmente estressante e os profissionais podem apresentar risco acentuado para sofrer desgastes biopsíquicos, com alteração de parâmetros fisiológicos e consequente elevação tensional. A detecção das variações de pressão arterial e de outros parâmetros hemodinâmicos ao longo dos períodos de trabalho e de descanso pode ser de extrema valia na detecção do risco cardiovascular nesta população. Este estudo de abordagem quantitativa, do tipo descritivo e transversal, teve por objetivo identificar o efeito do estresse laboral sobre o comportamento da pressão arterial de profissionais de enfermagem atuantes em um Centro de Terapia Intensiva por meio da avaliação de parâmetros clínicos obtidos pela Monitorização Ambulatorial da Pressão Arterial. Fizeram parte da amostra os integrantes da equipe de enfermagem lotados no Centro de Terapia Intensiva de um hospital do interior paulista. As variáveis investigadas foram: idade, gênero, cor da pele, escolaridade, situação familiar conjugal, profissão, ocupação, peso, estatura, circunferência abdominal, carga pressórica, média pressórica, pressões arteriais máximas e mínimas, frequência cardíaca, pressão de pulso e estresse percebido. A Monitorização Ambulatorial da Pressão Arterial foi realizada em dois momentos, sendo feito um exame no período de descanso e outro no período do trabalho. A frequência de estresse auto-referido foi verificada por meio da utilização da Escala Visual de Faces, nos períodos de trabalho e descanso. As análises descritivas, com cálculo de frequências absolutas e porcentagens, foram realizadas por meio do pacote estatístico Statistical Package for Social Science - SPSS, versão 15.0. Foi utilizado o teste de Wilcoxon para amostras pareadas. Os resultados foram expressos como médias ± erros padrões das médias (EPM) e as diferenças consideradas estatisticamente significantes para p<0,05. A coleta de dados foi realizada no período de agosto a outubro de 2012. Participaram do estudo 14 integrantes da equipe de enfermagem (28,6% enfermeiros, 21,4% técnicos de enfermagem e 50% auxiliares de enfermagem). A média de idade dos participantes foi igual a 33,14 ± 1,83 anos. O tempo de formação profissional foi de 9,14 ± 1,80 anos e o tempo de atuação em Centro de Terapia Intensiva igual a 6,09 ± 1,81 anos. A carga horária de trabalho semanal foi equivalente a 34,00 ± 1,50 horas/indivíduo. A média dos valores de Índice de Massa Corporal foi igual a 34,57± 2,19 Kg/m2 . Em relação aos valores de circunferência abdominal, a maioria dos indivíduos foi classificada na categoria \"risco substancialmente aumentado\", com média de 105,2 ± 7,03 cm. No período de trabalho, observou-se elevação da pressão arterial média, pressão arterial sistólica, pressão arterial diastólica, frequência cardíaca, pressão arterial sistólica máxima e mínima e pressão arterial diastólica máxima e mínima, com diferença estatisticamente significante (p<0,05) quando os valores foram comparados aos parâmetros obtidos no período de descanso. Sinais positivos de estresse foram referidos apenas no período de trabalho, por 29% dos entrevistados. Os resultados desse estudo evidenciaram que, durante o período de trabalho em Centro de Terapia Intensiva, os profissionais de enfermagem apresentam alterações de parâmetros clínicos e frequência aumentada de sinais positivos de estresse percebido. A elevação dos indicadores clínicos, atrelada ao relato de maior estresse no período de trabalho, sugere que os fatores ambientais são impactantes e amplificam o risco cardiovascular destes trabalhadores / Stress is understood as the product of man\'s relationship with the environment. A stressful event can trigger a set of physiological reactions that can lead to body imbalance. Health services provide working conditions which admittedly may cause tension. Nursing teams\' work in Intensive Care Units is potentially stressful and professionals may present increased risk to suffer biopsychic wearing, with altered physiological parameters and consequent increased tension. The detection of changed blood pressure and other hemodynamic parameters over periods of work and rest can be extremely valuable to detect cardiovascular risk in this population. This quantitative, descriptive and cross-sectional study aimed to identify the effect of job stress on blood pressure behavior of nursing professionals working in an Intensive Care Unit. Clinical parameters obtained by Ambulatory Blood Pressure Monitoring. The sample consisted of members of the nursing team working in the Intensive Care Unit of a hospital in the interior of the state of São Paulo. The following variables were studied: age, gender, skin color, education, marital status, profession, occupation, weight, height, waist circumference, blood pressure load, mean pressure, maximum and minimum blood pressures, heart rate, pulse pressure and perceived stress. Ambulatory Blood Pressure Monitoring was carried out in two phases, one examination was done during rest period and another during the work. The frequency of self-reported stress was verified by the use of Visual Faces Scale, the periods of work and rest. Descriptive analysis, with calculation of absolute and percentage frequencies, were performed using the Statistical Package for Social Sciences - SPSS, version 15.0. Wilcoxon test was used for paired samples. Results were expressed as means ± standard error of the mean (SEM) and differences were considered statistically significant at p<0.05. Data collection was carried out from August to October 2012. Participants were 14 members of the nursing team (28.6% nurses, 21.4% nursing technicians and 50% nursing auxiliaries). The average age of participants was 33.14 ± 1.83 years. Time from professional training was 9.14 ± 1.80 years and the time of work in the Intensive Care Unit was 6.09 ± 1.81 years. Weekly workload was equivalent to 34.00 ± 1.50 hours/worker. The mean values of Body Mass Index were 34.57 ± 2.19 kg/m2. Regarding the values of waist circumference, most individuals were classified in the category \"substantially increased risk\", with an average of 105.2 ± 7.03 cm. During the work, there was an increase in mean blood pressure, systolic blood pressure, diastolic blood pressure, heart rate, maximum and minimum systolic blood pressure and maximum and minimum diastolic blood pressure, with statistically significant difference (p<0.05) when the values were compared with the parameters obtained during rest period. Positive signs of stress were reported only during work period, by 29% of the respondents. Study results showed that during the period of work in the Intensive Care Unit nursing workers have changes in clinical parameters and increased frequency of positive signs of perceived stress. Increase in clinical indicators, associated to the report of greater stress during work, suggests that environmental factors are impacting and amplify the cardiovascular risk of these workers

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2016-04-01T20:14:11Z No. of bitstreams: 2 Dissertação - Aline Andrade Mourão - 2015.pdf: 2000857 bytes, checksum: 1da1abfc4f16d1970615dc3393d09323 (MD5) license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-04-04T14:50:45Z (GMT) No. of bitstreams: 2 Dissertação - Aline Andrade Mourão - 2015.pdf: 2000857 bytes, checksum: 1da1abfc4f16d1970615dc3393d09323 (MD5) license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) / Made available in DSpace on 2016-04-04T14:50:45Z (GMT). No. of bitstreams: 2 Dissertação - Aline Andrade Mourão - 2015.pdf: 2000857 bytes, checksum: 1da1abfc4f16d1970615dc3393d09323 (MD5) license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) Previous issue date: 2015-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Studies have demonstrated that neurons in the median pre-optic nucleus (MnPO) play a key role in the organization of cardiovascular responses induced by changes in circulating volume mostly through their projections to the paraventricular nucleus (PVN) of the hypothalamus. PVN in turn, projects to the rostroventrolateral medulla (RVLM) one of the main generators nucleus of vascular sympathetic, renal and cardiac activity. However, the autonomic response of blocked of the MnPO and central pathways and / or mechanisms involved in these responses remains unknown. The present study sought to determine the involvement of the MnPO in cardiovascular and autonomic regulation in Wistar (WT) and spontaneously hypertensive rats (SHR). For these, rats of the lineages WT (n = 6) and SHR (n = 6), weighing between 250 and 300g were anesthetized with urethane (1.2 g / kg, iv.) after induction with halothane (2% in O2 100%). The right femoral artery and vein were cannulated for recording of mean arterial pressure (MAP), and infusion of drugs, respectively. Heart rate (HR) was calculated as instantaneous frequency signal electrocardiogram (ECG). The animals were positioned in a stereotaxic apparatus, and instrumented for recording renal sympathetic nerve activity (RSNA). The nanoinjections of saline (NaCl; 150 mM), kynurenic acid (glutamate receptor antagonist; 50 mM) and muscimol (GABA agonist; 4 mM) were also performed. As expected, saline nanoinjections did not change the values of MAP (WT: 0.4 ± 0.2 mmHg; SHR: 0.2 ± 0.4 mmHg), HR (WT: 0.7 ± 0.9 bpm; SHR, 1.1 ± 1.4 bpm) and RSNA (WT: 0.4 ± 0.2%; SHR: 0.2 ± 1.3%). In WT (n=6) rats, the blockade of the MnPO with muscimol promoted fall in MAP (-17.0 ± 1.2 mmHg), bradycardia (-55,4 ± 12,3 bpm) and reduces in RSNA (-37.5 ± 3.9 %). The muscimol nanoinjections into the MnPO in SHR (n=6) promoted hypotension (-31.6 ± 5.0 mmHg), bradycardia (-18.3 ± 7.2 bpm), and renal sympathoinhibition (-54.4 ± 6.2 %). The changes in cardiovascular and autonomic parameters were evaluated in WT and SH rats submitted to sinoartic denervation. In normotensive rats, the inhibition of the MnPO by muscimol promoted decrease of MAP in innervated rats (n=6) and denervated (-19.4 ± 1.9 vs. 20.9 ± 4.3 mmHg, respectively; 3min; n=6), which was maintained throughout the experimental period (13.5 ± 2.0 vs. 22.5 ± 4.3 mmHg, 30 min). Also did not evidenced differences in RSNA in WT innervated (-23.0 ± 1.5%; 3min) and denervated (-21.0 ± 4.9%; 3min) rats. In denervated hypertensive rats (n=5), the blocked of MnPO resulted in progressive decrease in MAP (-31.1 ± 6.7, ± 9.7 and -38.7 ± 7.1 -44.7 mmHg, respectively 3, 15 and 30 min after MnPO blockade). The changes observed in the HR (-1.3 ± 3.3; -21.5 ± 12.6 and -24.9 ± 12.2 bpm, respectively 3, 15 and 30 min after MnPO blockade) and RSNA (-16.4 ± 8.8; -37.3 ± 10.1 and -45.1 ± 8.7%, respectively 3, 15 and 30 min after MnPO blockade) also followed this pattern of response. Finally to identify the involvement of glutamatergic neurotransmission in the MnPO on the cardiovascular and autonomic control, nanoinjections of kynurenic acid were performed in this nucleus. The glutamatergic blockade promoted decrease in MAP (WT: -18.2 ± 4.1 mmHg; SHR: -21.0 ± 2.5 mmHg), bradycardia (WT: -7.1 ± 1, 9 bpm; SHR: -9.0 ± 6.0 bpm) and renal simpathoinhibition (WT: -19.7 ± 2.4%; SHR: -24.7 ± 2.4%) in normotensive and hypertensive rats. In summary, the results obtained on this study demonstrated that acute blockade of MnPO reduces blood pressure (BP), confirming recent data that indicate that this nucleus participates of tonic control on BP. Our data suggest the involvement of MnPO the tonic regulation of sympathetic activity in WT and SHR. In addition, suggest the participation of this nucleus in increased sympathetic activity and consequent arterial blood pressure in SHR. The results demonstrated that aortic and carotid afferent participates in the modulation of autonomic and cardiovascular responses induced by blockade the MnPO in SHR. Furthermore, our data suggest that glutamatergic neurotransmission in the MnPO is important for the tonic regulation of BP, HR and RSNA thus, bringing new evidence that this nucleus participates of the autonomic and cardiovascular control. / Estudos têm demonstrado que os neurônios do núcleo pré-óptico mediano (MnPO) desempenham um importante papel na regulação cardiovascular e hidromineral, principalmente, por meio de suas projeções para o núcleo paraventricular (PVN) do hipotálamo. O PVN, por sua vez projeta-se para a região rostroventrolateral do bulbo (RVLM) um dos principais núcleos geradores da atividade simpática vascular, renal e cardíaca. Todavia, as respostas autonômicas frente a inibição do MnPO, bem como vias centrais e/ou mecanismos envolvidos nessas respostas permanecem desconhecidos. O presente estudo buscou determinar a participação do MnPO na regulação autonômica e cardiovascular em ratos wistar (WT) e espontaneamente hipertensos (SHR). Para tanto, ratos das linhagens WT e SHR, pesando entre 250 e 350g foram anestesiados com uretano (1,2 g/kg, iv.) após a indução com halotano (2% em O2 100%). A artéria e veia femorais direitas foram canuladas para o registro da pressão arterial média (PAM), e a infusão de drogas, respectivamente. A frequência cardíaca (FC) foi calculada como frequência instantânea do sinal de eletrocardiograma (ECG). Os animais foram posicionados em um aparelho estereotáxico e instrumentalizados para registro da atividade nervosa simpática renal (ANSR), e nanoinjeções (100nl) de soro fisiológico (NaCl; 150mM); ácido quinurênico (antagonista glutamatérgico; 50mM) e muscimol (agonista gabaérgico; 4mM) no MnPO. Como esperado, as nanoinjeções de soro não alteraram os valores da PAM (WT: 0,4 ± 0,2 mmHg; SHR: 0,2 ± 0,4 mmHg), FC (WT: 0,7 ± 0,9 bpm; SHR; 1,1 ± 1,4 bpm) e da ANSR (WT: 0,4 ± 0,2 %; SHR: -0,2 ± 1,3 %).Em ratos WT (n=6), o bloqueio farmacológico do MnPO com muscimol promoveu queda na PAM (-17,0 ± 1,2 mmHg), bradicardia (-55,4 ± 12,3 bpm) e redução na ANSR (-37,5 ± 3,9 %). As nanoinjeções de muscimol no MnPO dos SHR (n=6) promoveram hipotensão (-31,6 ± 5,0 mmHg), bradicardia (-18,3 ± 7,2 bpm), e simpatoinibição renal (-54,4 ± 6,2 %). As variações dos parâmetros autonômicos e cardiovasculares induzidas pela inibição do MnPO também foram avaliadas em ratos WT e SHR submetidos à desnervação dos aferentes sinoaórticos. Nos ratos normotensos, a inibição do MnPO com muscimol promoveu queda na PAM nos ratos inervados (n=6) e desnervados (-19,4 ± 1,9 vs. -20,9 ± 4,3 mmHg, respectivamente; 3min; n=6), sendo esta mantida por todo período experimental (-13,5 ± 2,0 vs. -22,5 ± 4,3 mmHg; 30min). Também não foram evidenciadas diferenças na redução da ANSR nos ratos WT inervados (-23,0 ± 1,5 %; 3min) e desnervados (-21,0 ± 4,9 %; 3min). Nos ratos hipertensos desnervados (n=5), o bloqueio do MnPO promoveu uma progressiva redução na PAM (-31,1 ± 6,7; -38,7 ± 9,7 e -44,7 ± 7,1 mmHg; respectivamente 3, 15 e 30 min após o bloqueio do MNPO). As alterações promovidas na FC (-1,3 ± 3,3; -21,5 ± 12,6 e -24,9 ± 12,2 bpm; respectivamente 3, 15 e 30 min após o bloqueio do MNPO) e ANSR (-16,4 ± 8,8; -37,3 ± 10,1 e -45,1 ± 8,7 %; respectivamente 3, 15 e 30 min após o bloqueio do MNPO) também seguiram esse padrão de resposta. Por fim para identificarmos a participação da neurotransmissão glutamatérgica no MnPO sobre o controle cardiovascular e autonômico, nanoinjeções de ácido quinurênico foram realizadas neste núcleo. O bloqueio glutamatérgico no MnPO promoveu queda na PAM (WT: -18,2 ± 4,1 mmHg vs. SHR: -21,0 ± 2,5 mmHg), bradicardia (WT: -7,1 ± 1,9 bpm vs. SHR: -9,0 ± 6,0 bpm e simpatoinibição renal (WT: -19,7 ± 2,4 % vs. SHR: -24,7 ± 2,4 %). Em conjunto, os resultados obtidos nesse estudo demonstraram que o bloqueio agudo do MnPO reduz a pressão arterial (PA), corroborando com dados recentes que indicam que esse núcleo participa do controle tônico da PA. Nossos dados sugerem o envolvimento do MnPO na regulação tônica da atividade simpática em WT e SHR. Ademais, sugerem a participação desse núcleo no aumento da atividade simpática e consequente hipertensão arterial observada em SHR. Os resultados evidenciaram ainda, que os aferentes aórticos e carotídeos participam na modulação das respostas autonômicas e cardiovasculares induzidas pelo bloqueio do MnPO em SHR. Além disso, nossos dados sugerem que a neurotransmissão glutamatérgica no MnPO é importante para a regulação tônica da PA, FC e ANSR trazendo assim novas evidências de que esse núcleo participa do controle autonômico e cardiovascular.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-03-06T17:42:24Z No. of bitstreams: 2 Dissertação - Stéfanne Madalena Marques - 2017.pdf: 2931392 bytes, checksum: 0d7549b7390188445fbcb19cb5e18723 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-07T10:42:02Z (GMT) No. of bitstreams: 2 Dissertação - Stéfanne Madalena Marques - 2017.pdf: 2931392 bytes, checksum: 0d7549b7390188445fbcb19cb5e18723 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-03-07T10:42:02Z (GMT). No. of bitstreams: 2 Dissertação - Stéfanne Madalena Marques - 2017.pdf: 2931392 bytes, checksum: 0d7549b7390188445fbcb19cb5e18723 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-17 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Several studies have determined the importance of intravenous infusion of sodium chloride (NaCl) solution in the cardiovascular recovery of hypovolemic hemorrhage (HH). Studies show the increased activity of the noradrenergic groups A1 and A2 in response to increased osmolarity in normovolemic rats. However, the participation of these neurons in the integration of the reflexive responses that lead to hemodynamic recovery and to the cardiovascular improvement induced by the infusion of hypertonic saline (HSI) solution during hypovolemia remain to be clarified. The present study sought to elucidate the participation of the noradrenergic groups A1 and A2 in cardiovascular recovery by HSI after HH in anesthetized rats. For this, mice should receive nanoinjections of 100 nL saporin (0.022 ng ∙ nl-1) or saporin-anti-DβH (0.105 ng ∙ nl-1) in the NTS region and/or bilaterally in the CVLM. After 20 days, the animals were instrumented to record the cardiovascular parameters: mean arterial pressure (MAP), heart rate (HR), renal vascular conductance (RVC), and aortic vascular conductance (AVC). HH was induced for 20 min by withdrawal of blood until a MAP reached about 60 mm Hg. Then, HIS (NaCl, 3M, 1.8 ml ∙ kg-1) / Diversos estudos determinaram a importância da infusão intravenosa de solução de cloreto de sódio (NaCl) hipertônica na recuperação cardiovascular da hemorragia hipovolêmica (HH). Estudos mostraram o aumento de atividade dos grupamentos noradrenérgicos bulbares A1 e A2 em resposta ao aumento da osmolaridade em ratos normovolêmicos. No entanto, a participação destes neurônios na integração das respostas reflexas que conduzem ao restabelecimento hemodinâmico e à melhora cardiovascular induzida pela infusão de solução salina hipertônica (SH) durante a hipovolemia ainda permanecem por ser esclarecidas. O presente estudo procurou elucidar a participação dos grupamentos noradrenérgicos bulbares A1 e A2 na recuperação cardiovascular por infusão de SH após HH em ratos anestesiados. Para isto, ratos Wistar receberam nanoinjeções de 100 nL de saporina (0,022 ng ∙ nl-1) ou saporina-anti-DβH (0,105 ng ∙ nl-1) na região NTS e/ou bilateralmente no CVLM. Após 15 dias, os animais foram instrumentalizados para registro dos parâmetros cardiovasculares: pressão arterial média (PAM), frequência cardíaca (FC), condutância vascular renal (CVR) e condutância vascular aórtica (CVA). A HH foi induzida durante 20 min pela retirada de sangue até que a PAM atingisse aproximadamente 60 mmHg. Em seguida, foi realizada a administração de solução SH (NaCl; 3M; 1,8 ml ∙ kg-1), e os parâmetros cardiovasculares foram registrados por mais 60 min. Os resultados mostraram que, nos animais com lesão do grupamento A2, após a infusão de SH a PAM retornou aos valores basais de maneira similar ao que ocorreu nos animais controle (sham A2: 109,4 ± 3,7 mmHg vs. Lesão A2: 108,6 ± 5,1 mmHg, 60 min após a infusão de SH); a FC reduziu significativamente em ratos controle e com lesão de A2 durante a HH e retornou aos níveis basais 10 min após infusão de SH (controle A2: 406,0 ± 10,6 bpm vs. Lesão A2: 368.8.1 ± 17,9 bpm); a HH e a infusão de solução SH não promoveu alterações nos valores basais de CVR em ambos os grupos (sham A2: Δ 3,0 ± 22,3%; Lesão A2: Δ -23,5 ± 16,6%, 20 min após a HH) e (sham A2: Δ 2,3 ± 18,8 vs. Lesão A2: Δ 7,3 ± 8,3%; 30 min após a infusão de SH). A CVA não foi alterada pela HH (sham A2: Δ -11,1 ± 6,6% vs Lesão A2: Δ 7,8 ± 11,6%; 20 min após a HH) ou infusão de SH (Sham: Δ -20,6 ± 7,8% vs. Lesão A2: Δ -4,4 ± 5,1%, 30 min após a infusão de SH). Nos animais com lesão combinada dos grupamentos A1 e A2, a infusão de SH não reestabeleceu os níveis de PAM (controle A1+A2: 104,9 ± 5,7 vs Lesão A1+A2: 64,2 ± 4,5 mmHg; p <0,05; 30 min após a infusão SH), permanecendo estes em níveis hemorrágicos até o final dos experimentos (controle A1+A2: 107,1 ± 3,3 vs Lesão A1+A2: 68,4 ± 4,2 mmHg; p <0,05; 60 min após infusão SH). A HH não alterou os valores basais de CVR (Sham A1+A2: Δ 4,7 ± 20,2% vs. Lesão A1+A2: Δ 2,9 ± 16,7%; 20 min após a HH); a solução SH, também, não foi capaz de alterar esse parâmetro nos grupos de animais controle e lesado (sham A1+A2: Δ: 0,1 ± 12,1% vs. Lesão A1+A2: Δ 29,4 ± 25,9%; 30 min após a infusão de SH). No grupo submetido a lesão A1+A2, a CVA não foi alterada pela HH em ambos os grupos (sham A1+A2: Δ -1,5 ± 16.3% vs. Lesão A1+A2: Δ -18,6 ± 6,3%; 20 min após a HH) ou pela infusão de solução de SH (sham A1+A2: Δ 20 ± 117% vs. Lesão A1+A2: Δ 9,5 ± 7,7%; 30 min após a infusão de SH). Os resultados indicam que o grupamento neuronal A2 não parece estar diretamente envolvido na recuperação cardiovascular por infusão de SH em ratos submetidos a HH e que a lesão simultânea dos grupamentos A1 e A2 foi capaz de suprimir a restauração da PAM em resposta à SH após a HH, indicando que a integridade desses grupamentos é essencial para a recuperação cardiovascular mediante hipernatremia aguda após a hipovolemia. Nosso estudo indica ainda que esses grupamentos não parecem estar diretamente envolvidos na regulação da reatividade vascular dos leitos analisados.