Efeitos da angiotensina-(1-7) endógena no núcleo paraventricular do hipotálamo nas alterações cardiovasculares que ocorrem durante as diferentes fases da hemorragia

Abstract

To characterize the cardiovascular effects mediated by the PVN, to evaluate the endogenous actions of the peptides with greater biological action of the RAS, before, during and after the hemorrhage, Wistar rats were submitted to bilateral microinjection of Muscimol, A779 and Losartan (gabaergic agonist, receptor antagonist Angiotensin- (1-7) MA and angiotensin II AT1 receptor antagonist, respectively). Bleeding was performed in a fixed volume of 24 mL/kg for 20 min in animals that were awake and freely moving. In addition to changes in MAP and HR parameters, autonomic function was analyzed through HR and SBP variability by spectral analysis. The involvement of peripheral vasopressin in the effects of A779 on PVN was also evaluated. Muscimol microinjection anticipated the BP drop induced by the hemorrhage, attenuated its decrease at the end of the hemorrhage and impaired the final phase of BP recovery. Losartan microinjection resulted in attenuation of the BP drop at the end of the hemorrhage, more agile BP recovery during recovery, sufficient to return to baseline values. Rats treated with A779 showed a similar result of attenuation of the drop in BP at the end of the hemorrhage but accompanied by tachycardia. This effect was abolished with i.v. of the V1 receptor antagonist. Rats treated with A779 also showed less variation in heart rate at the end of the hemorrhage, with no increase in LF and HF components during this period. They also presented greater BP lability during the entire hemorrhage, however, lower than that presented in the control group, which normalized in the recovery phase. The activity of nitric oxide synthase at the end of the hemorrhage was also evaluated through histochemical analysis, however there was no significant difference in the number of NADPH-diaphorase positive neurons between the Salina and A779 groups. Thus, this study suggests that the PVN plays a fundamental role in the modulation of blood pressure, especially in the compensated and recovery phases. The RAS peptides Angiotensin II and Ang-(1-7) acting in this nucleus, perform a modulating response related to the drop in blood pressure in the decompensated and recovery phases. Ang-(1-7), the peptide that was the focus of the study, modulates blood pressure possibly by reducing vagal tonus and the synthesis or release of vasopressin.