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 kidneys. Intrarenal infusion of endothelin (1 ng min-1 kg-1 body wt) reduced 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 constriction 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 infusion. During ureteral occlusion the inhibitory effect of endothelin on renin release either during inhibition of beta-adrenergic activity with propranolol or after inhibiting prostaglandin synthesis by indomethacin during intrarenal infusion of isoproterenol was examined. After propranolol administration ureteral occlusion increased renin release from 5 +/- 2 mug AI min-1 to 38 +/- 12 mug AI min-1 in six dogs. Subsequent intrarenal endothelin infusion (1 ng min-1 kg-1 body wt) during maintained ureteral occlusion reduced renin release to 10 +/- 3 mug AI min-1. In six other dogs prostaglandin synthesis was inhibited by indomethacin. Subsequent infusion of isoproterenol (0.2 mug min-1 kg-1 body wt) to stimulate beta-adrenoceptor activity increased renin release from 13 +/- 4 mug AI min-1 to 68 +/- 8 mug AI min-1 during ureteral occlusion. Intrarenal endothelin infusion (1 ng min-1 kg-1 body wt) reduced renin release to 22 +/- 3 mug AI min-1 during continuous isoproterenol infusion and ureteral occlusion. Hence endothelin inhibits renin release induced by renal arterial constriction or ureteral occlusion. Similar inhibitory effects whether renin release was raised by increasing prostaglandin synthesis or by stimulating beta-adrenergic activity suggest a direct effect of endothelin on the juxtaglomerular cells.