EFFECTS OF ENDOTHELINS ON RENIN SECRETION FROM ISOLATED MOUSE RENAL JUXTAGLOMERULAR CELLS

This study was performed to examine the effects of endothelin (ET)-1, ET-2, and ET-3 on renin secretion from cultured mouse renal juxtaglome rular (JG) cells. Although different ETs had no consistent effect on b asal renin secretion, they equipotently inhibited adenosine 3',5'-cycl ic monophosphate (cAMP)-stimulated renin release with a concentration of similar to 3 nM inhibiting 50% of maximal response. ETs did not sig nificantly affect renin release stimulated by the nitric oxide donor s odium nitroprusside (100 mu M) or that stimulated by low [2 mM ethylen e glycol-bis(P-aminoethyl ether)-N,N,N',N'-tetraacetic acid] or high ( 3 mM CaCl2) extracellular calcium. The inhibitory effect of ETs on cAM P-dependent renin secretion was abolished by lowering extracellular ca lcium concentration to the nanomolar range. However, the action of ETs was not changed by the ET(A) receptor antagonist BQ-123 (100 nM) and was mimicked by ET(B) receptor agonists IRL-1620 (1 mu M), sarafotoxin S6b (1 mu M), and [Ala(1,3,11,15)]ET-1 (1 mu M). All ETs induced calc ium oscillations in JG cells that were dependent on extracellular calc ium and were associated with prominent calcium-activated chloride curr ents. These findings suggest that ETs inhibit rather selectively the c AMP-activated pathway of renin secretion through a calcium-sensitive p rocess. The action of ETs on renal JG cells appears to be mediated via ET(B) receptors and is presumably related to activation of phospholip ase C and subsequent events.