ROLE OF BRADYKININ IN THE REGULATION OF BLOOD PRESSURE AND RENAL HEMODYNAMICS.

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To examine a possible role of endogenous bradykinin in the regulation of blood pressure(BP) and renal blood flow(RBF), a competitive antagonist of bradykinin(B4147) was studied in anesthetized Sprague Dawley(SD) rats, spontaneously hypertensive rats(SHR), DOCA salt hypertensive rats and Japanese albino rabbits. In SD rats, the intravenous infusion of B4147 inhibited the depressor effect of exogenous bradykinin by 69%. After an injection of B4147 at a dose of 25-100 mug in SD rats, BP increased and RBF decreased in a dose dependent fashion. The increase in BP was not blocked by treatment with angiotensin 11 antagonist or alpha_1-blocker. The administration of captopril decreased BP significantly. However, the injection of B4147 after the administration of captopril elicited an increase in BP of 43% of the initial decrease induced by captopril. These results suggest that the effects of B4147 on BP and RBF are not mediated through angiotensin 11 or sympathetic alpha_1-stimulation. Exogeno … More us bradykinin could contribute to the maintenance of BP and RBF in SD rats. Furthermore, bradykinin may partly participate in the acute hypotensive effect induced by the converting enzyme inhibitor captopril. In SHR, the magnitude in the change in BP was significantly lower in SHR than in control(WKY). The reduction of RBF was greater in WKY than in SHR. Bradykinin contributes to the maintenance of BP and RBF in both strains. However, deficiency in the bradykinin system in SHR may contributes partly to the development or the maintenance of hypertension. In DOCA-hypertensive rats, the magnitude of the increase in BP was significantly lower in DOCA hypertensive rats. The extent of the fall in RBF was reduced in DOCA hypertensive rats compared with control. These results suggest that endogenous bradykinin is depressed in the established phase of hypertension in DOCA-hypertensive rats. After the administration of bradykinin antagonist into the renal artery in anesthetized rabbits, both RBF and GFR were decreased significantly. These results indicate that endogenous kinins may participate in the regulation of RBF and GFR. Less