INHIBITORY EFFECT OF ENDOTHELIN ON RENIN RELEASE IN DOG KIDNEYS

To investigate the effect of endothelin on renin release, experiments were performed in barbiturate-anaesthetized dogs with denervated kidne ys. Intrarenal infusion of endothelin (1 ng min-1 kg-1 body wt) reduce d renal blood flow (RBF) from 145 +/- 10 ml min-1 to 98 +/- 9 ml min-1 without altering renin release (1 +/- 1 mug angiotensin I (AI) min-1) . Renin release was then increased either by renal arterial constricti on or ureteral occlusion. When renal arterial pressure was reduced to 50 mmHg, renin release averaged 79 +/- 20 mug AI min-1 in six dogs and fell significantly to 24 +/- 6 mug Al min-1 during endothelin infusio n. During ureteral occlusion the inhibitory effect of endothelin on re nin release either during inhibition of beta-adrenergic activity with propranolol or after inhibiting prostaglandin synthesis by indomethaci n during intrarenal infusion of isoproterenol was examined. After prop ranolol administration ureteral occlusion increased renin release from 5 +/- 2 mug AI min-1 to 38 +/- 12 mug AI min-1 in six dogs. Subsequen t intrarenal endothelin infusion (1 ng min-1 kg-1 body wt) during main tained ureteral occlusion reduced renin release to 10 +/- 3 mug AI min -1. In six other dogs prostaglandin synthesis was inhibited by indomet hacin. Subsequent infusion of isoproterenol (0.2 mug min-1 kg-1 body w t) to stimulate beta-adrenoceptor activity increased renin release fro m 13 +/- 4 mug AI min-1 to 68 +/- 8 mug AI min-1 during ureteral occlu sion. Intrarenal endothelin infusion (1 ng min-1 kg-1 body wt) reduced renin release to 22 +/- 3 mug AI min-1 during continuous isoprotereno l infusion and ureteral occlusion. Hence endothelin inhibits renin rel ease induced by renal arterial constriction or ureteral occlusion. Sim ilar inhibitory effects whether renin release was raised by increasing prostaglandin synthesis or by stimulating beta-adrenergic activity su ggest a direct effect of endothelin on the juxtaglomerular cells.