ENDOTHELIUM-MEDIATED REGULATION OF RENIN SECRETION

Endothelium-mediated regulation of renin secretion. The aim of the pre sent study was to investigate the endothelial influence on renin secre tion of isolated juxtaglomerular cells. Specifically the role of nitri c oxide (NO) and of endothelin was studied. Coculture of primary cultu res of juxtaglomerular cells with aortic and microvascular endothelial cells decreased renin secretion. Inhibition of NO formation by absenc e of l-arginine or presence of N omega-nitro-1-arginine caused a marke d decrease in cGMP accumulation and a reduction in renin secretion in cocultures. Exogenous NO (NO liberators sodium nitroprusside/SIN 1) st imulated the 20-hour renin secretion from juxtaglomerular cells marked ly, too. The effect of NO on renin secretion was biphasic: short-time inhibition and long-time stimulation of renin release. NO's stimulator y effect on renin secretion is dependent on extracellular calcium, but independent of cAMP or cGMP accumulation. Endothelin 1, 2, and 3 did not affect basal renin secretion, but inhibited cAMP stimulated renin release to a similar extent. Endothelin's action is not mediated via t he subtype A endothelin receptor, but seems to involve calcium mobiliz ation in juxtaglomerular cells that is dependent on extracellular calc ium and associated with prominent calcium activated chloride channels. Taken together, coculture of juxtaglomerular cells with endothelial c ells inhibits renin secretion despite the stimulatory effect of native NO released from endothelial cells. cAMP stimulated renin secretion i s inhibited by all three endothelin isoforms thus contributing to the inhibition of renin secretion in coculture.