RESUMO
INTRODUCTION: The present study was designed to determine the effects of selective antagonists of angiotensin II receptor types AT(1) and AT(2) on the flow of urine and sodium excretion induced by arginine vasopressin (AVP). MATERIALS AND METHODS: To this end, the drugs were microinjected into the medial septal area (MSA) of the brains of male Holtzman rats. Intravenous infusion of hypotonic saline was used to promote urinary flow, which was collected for one hour. RESULTS: MSA microinjections of AVP decreased the urinary flow and increased sodium excretion in a dose-dependent manner. Microinjection into MSA of an AT(2) antagonist (PD-123319) had a significantly greater effect than with an AT(1) antagonist (losartan) in increasing urinary flow and decreasing sodium excretion. These effects were more pronounced when both antagonists were injected together, before the AVP. CONCLUSIONS: These results indicate that MSA AT(1) and AT(2) receptors act synergistically in the regulation of urine and sodium excretion induced by AVP.
Assuntos
Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Septo do Cérebro/metabolismo , Sódio/urina , Vasopressinas/farmacologia , Animais , Masculino , Microinjeções , Ratos , Septo do Cérebro/efeitos dos fármacos , Septo do Cérebro/patologia , Micção/efeitos dos fármacosRESUMO
Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125,0 mg and zolazepan chloridrate 125,0 mg) into quadriceps muscle and submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 microg/0.5 microl), a nitric oxide (NO) donor, and N(W)-nitro-L-arginine methyl ester (L-NAME) 40 microg/0.5 microl, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Hipotálamo Médio/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Nitrocompostos/farmacologia , Área Pré-Óptica/efeitos dos fármacos , Sódio/urina , Animais , Ingestão de Líquidos/efeitos dos fármacos , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Injeções , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Natriurese/fisiologia , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/farmacologia , Nitrocompostos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
In this study we investigated the influence of d(CH2)5-Tyr(Me)-[Arg8]vasopressin (AAVP) and [adamanteanacetyl1,0-ET-d-Tyr2,Val4,aminobutyryl6,Arg8,9]-[Arg8]vasopressin (ATAVP), which are antagonists of vasopressin V1 and V2 receptors, and the effects of losartan, a selective angiotensin AT1 receptor antagonist, and CGP42112A, a selective AT2 receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg8]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT1 and AT2 ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT1 receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V1 receptors and that the inhibitory effect requires V2 receptors. The involvement of AT1 and AT2 receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance.