EFFECTS OF ENDOTHELINS ON RENIN SECRETION FROM RAT KIDNEYS

Using a preparation of isolated rat kidneys perfused at constant renal artery pressure (80 mmHg) we investigated the role of endothelins in the regulation of renin release. Addition of three related endothelins (ET-1, ET-2, ET-3) at a concentration of 10 pmol L(-1) tended to enhance renin secretion rates. Higher doses (100 pmol L(-1), 1 nmol L(-1)) of different ETs such as the selective ET(B) receptor agonist sarafotoxin S6c (100 pmol L(-1), 1nmol L(-1)) inhibited renin release and increased renal vascular resistance with similar potency. These effects of ETs were blunted when calcium ions were removed from the perfusate. Renin release activated by isoproterenol (10 nmol L(-1)) was also significantly reduced with ET-1, -2 and -3 (1 nmol L(-1)). BQ-123 (500 nmol L(-1)), a selective ET(A) receptor antagonist, only attenuated, whilst the nonselective ET receptor blocker bosentan (Ro 47-0203, 10 mu mol L(-1)) almost abolished the renal vasopressor and renin inhibitory action of ET-1 and sarafotoxin S6c. BQ-123 and bosentan alone did not affect either perfusate flow or basal renin secretion rates in isolated perfused kidneys. These findings indicate that all three ET peptides equipotently inhibit renin secretion from the kidneys. Most of the vasopressor and renin inhibitory effect of ETs is mediated by ET(B) rather than ET(A) receptors involving a calcium-dependent signal transduction mechanism. Moreover, our results suggest that intrarenally released ETs do not contribute to the regulation of renin secretion from isolated perfused rat kidneys.