Imidazoline receptors of the paraventricular nucleus on the pressor response induced by stimulation of the subfornical organ

In the present experiments we investigated a possible involvement of imidazoline receptors of the paraventricular nucleus (PVN) of the hypothalamus on the presser effects of the angiotensin LI (ANG II) injected into the subfornical organ (SFO), in male Holtzman rats (250-300 g) with a cannula implanted into the third ventricle (3rdV), PVN and SFO. At first we tested the participation of alpha(2) and imidazoline agonist and antagonist compounds on the presser effect of ANG II injected into the 3rdV. Based on the results we may conclude that clonidine associated with rilmenidine was able to block the hypertensive response to ANG IT. The ANG II (20 pmol) injected into SFO induced a robust increase in blood pressure (37 +/- 2 mmHg). Isotonic saline (0.15 M) NaCl did not produce any change in blood pressure (5 +/- 2 mmHg). The injection of rilmenidine (30 mu g/kg/l mu L), an imidazoline agonist agent injected into PVN before ANG II injection into SFO, blocked the presser effect of ANG II (5 +/- 2 mmHg). Also, the injection of idazoxan (60 mu g/kg/mu L) before rilmenidine blocked the inhibitory effect of rilmenidine on blood pressure (39 +/- 4 mmHg). The injection of clonidine (20 nmol/mu L) prior to ANG II into the 3rdV produced a decreased in arterial blood pressure (37 +/- 2 mmHg) to (15 +/- 4 mmHg). The injection of yohimbine (80 nmol/mu L) prior to clonidine blocked the effect of clonidine on the effect of ANG II (27 +/- 2 mmHg). The injection of rilmenidine prior to ANG TI also induced a decrease in arterial blood pressure (10 +/- 3 mmHg). The injection of idazoxan prior to rilmenidine also blocked the inhibitory effect of rilmenidine (24 +/- 3 mmHg). In summary, the present study demonstrated that rilmenidine decreases the hypertensive effect of ANG II, with more potency than clonidine, even when injected into 3rdV or PVN. This study established that the PVN interacts with SFO by imidazoline receptors in order to control the arterial blood pressure. (C) Elsevier, Paris.

Functional relationship between subfrnical organ cholinergic stimulation and nitrergic activation influencing cardiovascular and body fluid homeostasis

We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO). Rats (Holtzman 250-300 g) were anesthetized with 2, 2, 2-tribromoethanol (20 mg/100 kg b. wt.) and a stainless steel carmula were implanted into their SFO. The volume of injection was 0.2 mu l. The amount of saliva secretion was studied over a 5-min period. Pilocarpine (40 mu g), L-NAME (40 mu g) and LAR (30 mu g) were used in all experiments for the injection into the SFO. Pilocarpine (10, 20, 40, 80 and 160 mu g) injected into SFO elicited a concentration-dependent increase in salivary secretion. L-NAME injected prior to pilocarpine into the SFO increased salivary secretion and water intake due to the effect of pilocarpine. LAR injected prior to pilocarpine into the SFO attenuated the salivary secretion and water intake. Pilocarpine, injected into the SFO increased the MAP and decreased heart rate (HR). L-NAME injected prior to pilocarpine into the SFO potentiated the pressor effect of pilocarpine with a decrease in HR. LAR injected into the SFO prior to pilocarpine attenuated the increase in MAP with no changes in HR. The present study suggests that the SFO nitrergic cells interfere in the cholinergic pathways implicated in the control of salivary secretion, fluid and cardiovascular homeostasis. (c) 2007 Elsevier B.V All rights reserved.

Novel evidence that nitric oxide of the medial septal area influences the salivary secretion induced by pilocarpine

Our studies have focused on the effect of injection of L-NAME and sodium nitroprussiate (SNP) on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine which was injected into the medial septal area (MSA). Rats were anesthetized with urethane (1.25 g/kg b. wt.) and a stainless steel cannula was implanted into their MSA. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into MSA. Injection of pilocarpine (10, 20, 40, 80, 160 mug/mul) into MSA produced a dose-dependent increase in salivary secretion. L-NG-nitro arginine methyl-esther (L-NAME) (40 mug/mul), a nitric oxide (NO) synthase inhibitor, was injected into MSA prior to the injection of pilocarpine into MSA, producing an increase in salivary secretion due to the effect of pilocarpine. Sodium nitroprussiate (SNP) (30 mug/mul) was injected into MSA prior to the injection of pilocarpine into MSA attenuating the increase in salivary secretion induced by pilocarpine. Medial arterial pressure (MAP) increase after injections of pilocarpine into the MSA. L-NAME injected into the MSA prior to injection of pilocarpine into MSA increased the MAP. SNP injected into the MSA prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (40 mug/mul) injected into the MAS induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the MSA increased the urinary sodium excretion and urinary volume induced by pilocarpine. SNP injected prior to pilocarpine into the MSA decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the MSA. We may also conclude that the MSA is involved with the cholinergic excitatory mechanism that induce salivary secretion, increase in MAP and increase in sodium excretion and urinary volume. (C) 2002 Elsevier B.V. All rights reserved.

Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes

Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 +/- 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma Na+; 2) decreased blood volume; and 3) reduced total body Na+; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma Na+ concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water.

Lesions of the commissural subnucleus of the nucleus of the solitary tract increase isoproterenol-induced water intake

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT(1) and AT(2) angiotensin antagonist's receptors

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prevalence of metabolic syndrome in elderly Japanese-Brazilians

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Regulation of ventilation in the caiman (Caiman latirostris): effects of inspired CO2 on pulmonary and upper airway chemoreceptors

In order to study the relative roles of receptors in the upper airways, lungs and systemic circulation in modulating the ventilatory response of caiman (Caiman latirostris) to inhaled CO2, gas mixtures of varying concentrations of CO2 Were administered to animals breathing through an intact respiratory system, via a tracheal cannula by-passing the upper airways (before and after vagotomy), or via a cannula delivering gas to the upper airways alone. While increasing levels of hypercarbia led to a progressive increase in tidal volume in animals with intact respiratory systems (Series 1), breathing frequency did not change until the CO2 level reached 7%, at which time it decreased. Despite this, at the higher levels of hypercarbia, the net effect was a large and progressive increase in total ventilation. There were no associated changes in heart rate or arterial blood pressure. on return to air, there was an immediate change in breathing pattern; breathing frequency increased above air-breathing values, roughly to the same maximum level regardless of the level of CO2 the animal had been previously breathing, and tidal volume returned rapidly toward resting (baseline) values. Total ventilation slowly returned to air breathing values. Administration of CO2 via different routes indicated that inhaled CO2 acted at both upper airway and pulmonary CO2-sensitive receptors to modify breathing pattern without inhibiting breathing overall. Our data suggest that in caiman, high levels of inspired CO2 promote slow, deep breathing. This will decrease deadspace ventilation and may reduce stratification in the saccular portions of the lung.

Efeitos cardiorrespiratórios da tiletamina-zolazepam em cães hipovolêmicos

O objetivo deste estudo foi avaliar os efeitos da associação tiletamina-zolazepam em cães hipovolêmicos. Estudaram-se as alterações cardiovasculares em 14 cães, divididos em grupo A (controle, n=7) e grupo B (experimental, n=7). Os cães foram anestesiados com sevoflurano (1,5 concentração alveolar mínima - CAM) para a implantação dos cateteres venosos, arteriais e da termodiluição. A concentração do sevoflurano foi reduzida (0,5 CAM) e nos cães do grupo B, induziu-se hipovolemia retirando-se sangue na proporção de 30ml/kg de peso corpóreo. Subseqüentemente, registraram-se as freqüências cardíaca (FC) e respiratória (FR), a pressão arterial (PAM) e o débito cardíaco (DC), e aplicaram-se 10 mg/kg de tiletamina-zolazepam, pela via intravenosa. Aos cães do grupo A aplicou-se igual tratamento. Os cães foram observados por 120 minutos. A associação tiletamina-zolazepam produziu apnéia transitória e manteve estável a FC, PAM e DC. O resultados permitem concluir que a associação manteve estáveis as pressões arteriais sistólica, diastólica e média, e não alterou o débito cardíaco, podendo vir a ser usada com segurança na anestesia de cães com hipovolemia.

Efeitos cardiovasculares e neuroendócrinos do butorfanol e da buprenorfina em cães anestesiados pelo desfluorano

Avaliaram-se os efeitos do butorfanol e da buprenorfina sobre variáveis cardiovasculares e neuroendócrinas em cães anestesiados com desfluorano, utilizando-se 30 cães adultos, machos e fêmeas, distribuídos em três grupos denominados grupo butorfanol (GBT), grupo buprenorfina (GBP) e grupo-controle (GCO). A anestesia foi induzida com propofol (8mg/kgIV) e nos animais intubados administrou-se desfluorano (1,5CAM). Após 30 minutos, nos cães do GBT, aplicou-se butorfanol (0,4mg/kgIM); nos do GBP, buprenorfina (0,02mg/kgIM); e nos do GCO, solução de NaCl a 0,9% (0,05ml/kgIM). Avaliaram-se: freqüência cardíaca; pressões arteriais sistólica, diastólica e média; débito cardíaco; pressão venosa central; cortisol; hormônio adrenocorticotrópico; noradrenalina; e glicose. As colheitas dos dados foram feitas aos 30 minutos após o início da administração do desfluorano (M0), 15 minutos após a administração do opióide ou placebo (M15), e a cada 15 minutos após M15 (M30, M45, M60 e M75). Para a avaliação neuroendócrina utilizaram-se os momentos M-30 (antes da administração dos fármacos), M0, M15 e M45. Na freqüência cardíaca houve diferença entre M0 e M15 (129 e 111bat/min) em GBT, e entre M0 e M30 (131 e 112bat/min) em GBP. Na pressão arterial média, a diferença foi entre M0 (86mmHg) e todos os momentos que se seguiram (todos os valores foram menores que 72mmHg), em GBT. A pressão arterial diastólica foi menor em todos os momentos (<53mmHg) quando comparada com a do M0 (67mmHg), em GBT. Na pressão arterial sistólica, a diferença foi entre M0 e M15 e M30 (112 versus 93 e 94mmHg, respectivamente) em GBT. A inclusão dos opióides determinou discreta redução nos parâmetros cardiovasculares, enquanto o desfluorano interferiu na função neuroendócrina elevando os níveis plasmáticos de glicose.

Cardiovascular assessment in horses sedated with xylazine or amitraz

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeitos hemodinâmicos e metabólicos imediatos determinados pelas soluções de cloreto de sódio a 7,5% e de sua associação ao dextran 70 a 6% na reanimação do choque hemorrágico: estudo experimental em cães

JUSTIFICATIVA E OBJETIVOS: O dextran associado à solução hipertônica de cloreto sódio a 7,5% apresenta efeitos hemodinâmicos benéficos no controle prolongado da reanimação no choque hemorrágico. O objetivo deste estudo foi verificar se a associação do dextran à solução de cloreto de sódio a 7,5% apresentaria vantagens na avaliação imediata dos parâmetros hemodinâmicos e metabólicos na reanimação em modelo de choque hemorrágico controlado em cães. MÉTODO: Foram estudados 16 cães submetidos à hemorragia controlada até que a pressão arterial média atingisse 40 mmHg e permanecesse assim por até 30 minutos. Estes foram divididos em G1, com administração de NaCI a 7,5%, e G2, com administração NaCI a 7,5% combinada com dextran 70 a 6%, no volume de 4 mL.kg-1, durante três minutos. Foram avaliados os parâmetros hemodinâmicos e metabólicos. Consideraram-se quatro momentos: M1 - 10 minutos após o preparo cirúrgico, M2 - obtido na metade da fase de choque, M3 - obtido dois minutos após o final da administração das soluções, M4 - 30 minutos após o início da reanimação. RESULTADOS: Após a reanimação, não houve diferença significativa dos valores da FC, PAM, PCP e IRVS. O G2 apresentou valores maiores do IC em M4. Os valores da SvO2 foram menores no G1, final do experimento. A C(a-v)O2 foi maior no G1 nos momentos M3 e M4. Os valores do VO2 aumentaram nos dois grupos em M4 e os valores do lactato plasmático aumentaram progressivamente até M3 e diminuíram em M4. Houve aumento dos valores do Na plasmático e redução do hematócrito nos dois grupos. CONCLUSÕES: O G2 mostrou melhor desempenho hemodinâmico principalmente após 30 minutos do início da reanimação. Observou-se, também, maior expansão plasmática e melhor perfusão tecidual na associação do dextran ao NaCl a 7,5%.

Avaliação de dois modelos experimentais de isquemia e reperfusão cerebral em ratos com oclusão temporária carotídea associada ou não à oclusão vertebral

OBJETIVO: Avaliar a reprodutibilidade de dois modelos experimentais de isquemia e reperfusão cerebral. MÉTODOS: 60 ratos foram distribuídos, aleatoriamente, em três grupos experimentais, com 20 animais cada: I - pinçamento temporário de artéria carótida esquerda; II - cauterização prévia das artérias vertebrais e pinçamento temporário da artéria carótida esquerda; simulado - sem isquemia nem reperfusão. Todos os animais tiveram oclusão definitiva de artéria carótida direita e os três grupos foram subdivididos em dois períodos de reperfusão: A - 60 minutos e B - 120 minutos. Os parâmetros verificados foram: medidas de pressão arterial média sistêmica e fluxo sangüíneo carotídeo; medida de malondialdeído cerebral através do teste TBARS e avaliação histológica do hemisfério cerebral submetido à isquemia e reperfusão. Foi feito também um estudo complementar com angiografia cerebral em 5 animais adicionais. RESULTADOS: Não houve diferenças significativas nas dosagens de malondialdeído cerebral e na freqüência e gravidade das alterações histológicas cerebrais entre os três grupos. Nos grupos GI e GII, a PAM foi significantemente maior no período de isquemia. O fluxo sangüíneo entre os períodos pré e pós-pinçamento aumentou nos grupos IA e IIB, diminuiu no grupo IB e no grupo IIA manteve-se inalterado. As angiografias do estudo complementar mostraram aporte sangüíneo para cérebro através de circulação colateral. CONCLUSÃO: Os modelos de isquemia e reperfusão estudados não demonstraram alterações consistentes de marcadores de lesão cerebral, seja quanto à produção de lipoperóxidos ou de lesões histológicas.