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.