Inhibitory effect of endothelin on renin release in dog kidneys

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Abstract
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‐1kg‐1body wt) reduced renal blood flow (RBF) from 145 ± 10 ml min‐1to 98 ± 9 ml min‐1without altering renin release (1 ± 1μg 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 ± 20μg AI min‐1in six dogs and fell significantly to 24 ± 6μg AI min‐1during endothelin infusion. During ureteral occlusion the inhibitory effect of endothelin on renin release either during inhibition ofβ‐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 ± 2μg AI min‐1to 38 ± 12μg AI min‐1in six dogs. Subsequent intrarenal endothelin infusion (1 ng min‐1kg‐1body wt) during maintained ureteral occlusion reduced renin release to 10 ± 3μg AI min‐1. In six other dogs prostaglandin synthesis was inhibited by indomethacin. Subsequent infusion of isoproterenol (0.2μg min‐1kg‐1body wt) to stimulateβ‐adrenoceptor activity increased renin release from 13 ± 4μg AI min‐1to 68 ± 8μg AI min‐1during ureteral occlusion. Intrarenal endothelin infusion (1 ng min‐1kg‐1body wt) reduced renin release to 22 ± 3μg AI min‐1during 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 stimulatingβ‐adrenergic activity suggest a direct effect of endothelin on the juxtaglomerular cells.