RESUMO
OBJECTIVE: In the present study, the peripheral mechanism that mediates the pressor effect of angiotensin-(1-7) in the rostral ventrolateral medulla was investigated. METHOD: Angiotensin-(1-7) (25 pmol) was bilaterally microinjected in the rostral ventrolateral medulla near the ventral surface in urethane-anesthetized male Wistar rats that were untreated or treated (intravenously) with effective doses of selective autonomic receptor antagonists (atenolol, prazosin, methyl-atropine, and hexamethonium) or a vasopressin V1 receptor antagonist [d(CH2)5 -Tyr(Me)-AVP] given alone or in combination. RESULTS: Unexpectedly, the pressor response produced by angiotensin-(1-7) (16 ± 2 mmHg, n = 12), which was not associated with significant changes in heart rate, was not significantly altered by peripheral treatment with prazosin, the vasopressin V1 receptor antagonist, hexamethonium or methyl-atropine. Similar results were obtained in experiments that tested the association of prazosin and atenolol; methyl-atropine and the vasopressin V1 antagonist or methyl-atropine and prazosin. Peripheral treatment with the combination of prazosin, atenolol and the vasopressin V1 antagonist abolished the pressor effect of glutamate; however, this treatment produced only a small decrease in the pressor effect of angiotensin-(1-7) at the rostral ventrolateral medulla. The combination of hexamethonium with the vasopressin V1 receptor antagonist or the combination of prazosin, atenolol, the vasopressin V1 receptor antagonist and methyl-atropine was effective in blocking the effect of angiotensin-(1-7) at the rostral ventrolateral medulla. CONCLUSION: These results indicate that angiotensin-(1-7) triggers a complex pressor response at the rostral ventrolateral medulla that involves an increase in sympathetic tonus, release of vasopressin and possibly the inhibition of a vasodilatory mechanism.
Assuntos
Animais , Masculino , Ratos , Angiotensina I/farmacologia , Bulbo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Vasodilatadores/farmacologia , Angiotensina I/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hexametônio/administração & dosagem , Microinjeções , Bulbo/fisiopatologia , Fragmentos de Peptídeos/administração & dosagem , Ratos Wistar , Receptores de Vasopressinas/antagonistas & inibidores , Fatores de Tempo , Vasodilatadores/administração & dosagemRESUMO
Endothelial cells are directly involved in many functions of the cardiovascular system by regulating blood flow and blood pressure through Ca2+ dependent exocitosis of vasoactive compounds. Using the Ca2+ indicator Fluo-3 and the patch-clamp technique, we show that bovine adrenal medulla capillary endothelial cells (B AMCECs) respond to acetylcholine (ACh) with a cytosolic Ca2+ increase and depolarization of the membrane potential (20.3±0.9 mV; n=23). The increase in cytosolic Ca2+ induced by 10µM ACh was mimicked by the same concentration of nicotine but not by muscarine and was blocked by 100 µM of hexamethonium. On the other hand, the increase in cytosolic Ca2+ could be depressed by nifedipine (0.01 -100 µM) or withdrawal of extracellular Ca2+. Taken together, these results give evidence for functional nicotinic receptors (nAChRs) in capillary endothelial cells of the adrenal medulla. It suggests that nAChRs in B AMCECs may be involved in the regulation of the adrenal gland's microcirculation by depolarizing the membrane potential, leading to the opening of voltage-activated Ca2+ channels, influx of external Ca2+ and liberation of vasoactive compounds.
Assuntos
Animais , Bovinos , Medula Suprarrenal/efeitos dos fármacos , Canais de Cálcio/efeitos dos fármacos , Citosol/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Nicotina/farmacologia , Receptores Nicotínicos/efeitos dos fármacos , Acetilcolina/farmacologia , Medula Suprarrenal/irrigação sanguínea , Medula Suprarrenal/citologia , Canais de Cálcio/metabolismo , Capilares/citologia , Capilares/efeitos dos fármacos , Citosol/metabolismo , Potenciais Evocados/efeitos dos fármacos , Hexametônio/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Muscarina/farmacologia , Receptores Nicotínicos/metabolismoRESUMO
The use of colored microspheres to adequately evaluate blood flow changes under different circumstances in the same rat has been validated with a maximum of three different colors due to methodological limitations. The aim of the present study was to validate the use of four different colors measuring four repeated blood flow changes in the same rat to assess the role of vasopressor systems in controlling arterial pressure (AP). Red (150,000), white (200,000), yellow (150,000), and blue (200,000) colored microspheres were infused into the left ventricle of 6 male Wistar rats 1) at rest and 2) after vasopressin (aAVP, 10 æg/kg, iv), 3) renin-angiotensin (losartan, 10 mg/kg, iv), and 4) sympathetic system blockade (hexamethonium, 20 mg/kg, iv) to determine blood flow changes. AP was recorded and processed with a data acquisition system (1-kHz sampling frequency). Blood flow changes were quantified by spectrophotometry absorption peaks for colored microsphere components in the tissues evaluated. Administration of aAVP and losartan slightly reduced the AP (-5.7 ± 0.5 and -7.8 ± 1.2 mmHg, respectively), while hexamethonium induced a 52 ± 3 mmHg fall in AP. The aAVP injection increased blood flow in lungs (78 percent), liver (117 percent) and skeletal muscle (>150 percent), while losartan administration enhanced blood flow in heart (126 percent), lungs (100 percent), kidneys (80 percent), and gastrocnemius (75 percent) and soleus (94 percent) muscles. Hexamethonium administration reduced only kidney blood flow (50 percent). In conclusion, four types of colored microspheres can be used to perform four repeated blood flow measurements in the same rat detecting small alterations such as changes in tissues with low blood flow.
Assuntos
Animais , Masculino , Ratos , Anti-Hipertensivos/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Microesferas , Arginina Vasopressina/farmacologia , Cor , Débito Cardíaco/efeitos dos fármacos , Hexametônio/farmacologia , Losartan/farmacologia , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Espectrofotometria AtômicaRESUMO
The underlying mechanisms of acetycholine-induced intestinal relaxation in the lizard Liolaemus tenuis tenuis are still unknows. By using a classical model of intestinal recording of isometric contraction and relaxation in conjunction with specific pharmacological tools, this article studies the possible influence of EDRF/NO and nicotinic ganglionar receptors on the Ach-induced relaxation in an effort to elucidate the probable mechanisms involved in ACh effect. It was observed that the relaxation of the lizard intestine elicited by ACh (10(-7) - 4 x 10(-4) M) was not affected by hexametonium (5 x 10(4) M) or tetrodotoxin (10(-6) M). Nicotine (10(-7) to 10(-4) M) induced relaxation was significantly antagonized by hexametonium; however, it was not influenced by tetrodotoxin. These results allow us to discard a neuronal pathway in cholinergic-induced relaxation, suggesting a more direct cholinergic effect on the smooth muscle, perhaps mediated by an unknown substance released by some specialized tissue. N-nitro-L-arginine, used to block NO-synthase and NO production, induced no changes in ACh-induced relaxation. Methylene blue, a soluble guanylate cyclase inhibitor, induced no changes in ACh-induced relaxation. These results allow us to dicard a probable role of EDRF/nitric oxide in the ACh-induced relaxation of lizard small intestine, providing evidence that this mechanism could be different from reported on other species.
Assuntos
Animais , Masculino , Feminino , Agonistas Colinérgicos/farmacologia , Esôfago/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Tono Muscular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Hexametônio/farmacologia , Lagartos , Azul de Metileno/farmacologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Óxido Nítrico Sintase , Nitroarginina/farmacologia , Tetrodotoxina/farmacologiaRESUMO
A acetilcolina liberada do terminal nervoso motor (TNM) pode modular sua pr6pria liberagdo (automodulação do TNM), interagindo com receptores nicotinicos (autoestimulação do TNM) ou muscarinicos (autoinibição do TNM) pré-juncionais. Por outro lado, tem-se demonstrado que a neuropatia induzida pelo estado diabético determine vários danos estruturais no interior do TNM, sem, contudo, interferir na velocidade e na integridade da transmissão neuromuscular. Estudos farmacológicos demonstram que animais diabéticos, quando comparados aos normais, são menos sensíveis a alguns bloqueadores neuromusculares (d-tubocurarina, galamina, pancurônio e decametônio). Esses resultados sugerem que alguma modificação no sistema de automodulação do TNM pode contrabalançar as deficiências neuronais induzidas pelo estado diabético. Dessa forma, o presente estudo foi conduzido com preparações nervo frênico-diafragma isolado de ratos (obtidas de animais normais e diabéticos) na tentativa de verificar se existiriam diferenças na fadiga neuromuscular induzida por drogas (d-tubocurarina, neostigmina, hexametônio). Nossos resultados mostraram que, embora não existissem diferenças na indução da fadiga neuromuscular induzida por d-tubocurarina, neostigmina ou hexametônio, o recobro da fadiga neuromuscular induzida por d-tubocurarina foi mais rápido em preparações neuromusculares obtidas de animais diabéticos. Essa diferença pode estar relacionada a alguma modificação induzida pelo estado diabético que determinou redugio da afinidade da d-tubocurarina para os receptores nicotínicos pré-juncionais
Assuntos
Animais , Ratos , Trietiodeto de Galamina , Hexametônio/uso terapêutico , Neostigmina , Pancurônio/uso terapêutico , TubocurarinaRESUMO
O efeito da noradrenalina, isoproterenol, fentolamina e propanolol, injetados no núcleo basolateral da amigdala, sobre a ingestäo de água, foi investigado em ratos Holtzman. A injeçäo de noradrenalina (40nmol) no complexo amigdalóide (CA) de ratos saciados näo produziu nenhuma mudança na ingestäo de água em ratos saciados (1,93 ñ 0,23 ml/lh). A noradrenalina injetada no CA produziu uma diminuiçäo na ingestäo de água de ratos privados (0,40 ñ 0,19 ml/lh). A injeçäo de isoproterenol no CA de ratos privados näo produziu nenhuma mudança na ingestäo de água em comparaçäo aos controles (11,65 ñ 1,02 e 10,92 ñ 0,88 ml/lh, respectivamente). Quando comparado com valores controles, a fentolamina injetada prévia à noradrenalina bloqueou o efeito inibitório da noradrenalina sobre a ingestäo de água em ratos privados 10,40 ñ 1,31 ml/lh). O propanolol bloqueou o efeito do isorpoterenol em ratos saciados (0,85 ñ 0,49 ml/lh) e também bloqueou a ingestäo água induzida por privaçäo (0,53 ñ 0,38 ml/lh). Tanto em animais saciados quanto em privados, a injeçäo de fentolamina, antes da administraçäo de hexametônio, bloqueou o efeito inibitório do hexametônio na ingestäo de água. Em animais saciados, quando o hexametônio foi injetado sozinho, a ingestäo de água foi de 0,39 ñ 0,25 ml/lh; quando acompanhado de fentolamina, a ingestäo de água foi de 1,04 ñ 0,3 ml/lh. Em ratos privados, o hexametônio sozinho bloqueou a ingestäo de água (0,40 ñ 0,17 ml/lh) e quando injetado com fentolamina produziu uma ingestäo de 9,7 ñ 1,8 ml/lh. Este resultados demonstram claramente a participaçäo de receptores catecolaminérgicos do CA na regulaçäo da ingestäo de água.
Assuntos
Animais , Masculino , Ratos , Tonsila do Cerebelo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Líquidos , Isoproterenol/farmacologia , Norepinefrina/farmacologia , Fentolamina/farmacologia , Propranolol/farmacologia , Hexametônio/administração & dosagem , Ratos Endogâmicos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfaRESUMO
The effect of carbachol (80 nmol/microliters) injection into the amygdaloid nuclear complex (AMG) on sodium appetite and water intake was studied in male Holtzman rats weighing 240-270 g. Twenty-five satiated rats and 38 water-deprived rats were used in the experiment on water intake. In the experiment on sodium intake, 19 rats were injected with atropine+carbachol and 9 rats with hexamethonium+carbachol. After carbachol injection into the AMG, water intake decreased in rats submitted to 30 h of water deprivation (10.28 +/- 1.04 ml/120 min vs 0.69 +/- 0.22 ml/120 min). The decrease in water intake was blocked by prior local injection of atropine (20 nmol/l microliters) (11.66 +/- 1.46 ml/120 min vs 0.69 +/- 0.22 ml/120 min), but not of hexamethonium (30 nmol/1 microliters), into the AMG. In water-deprived animals, carbachol injection into the AMG caused a decrease in sodium chloride intake (6.16 +/- 1.82 ml/h vs 0.88 +/- 0.54 ml/h) which was blocked by previous injection of hexamethonium but not of atropine. These results suggest that the cholinergic system of the AMG plays a role in the control of water and salt intake.