Endothelin ET(B) receptor subtype mediates nitric oxide/cGMP formation in rat adrenal medulla

We investigated the effect of endothelins (ETs) on receptor-mediated cGMP formation in whole rat adrenal medulla. ET-3 increased cGMP formation in a concentration-dependent manner; in addition, all three isoforms of ETs, at equimolar doses, increased cGMP levels in similar degree. IRL-1620, a selective ET(B) receptor agonist, also increased cGMP formation, mimicking the effects of ETs, but the increase was higher than those produced by ETs. L-arginine analogue, N-nitro-L-arginine (L-NAME), and methylene blue and OQD, two inhibitors of soluble guanylyl cyclase, significantly inhibited the increase in cGMP production induced by ETs or IRL-1620. Likewise, the selective ET(B) receptor antagonist, BQ-788, significantly inhibited ET-1- or ET-3-induced cGMP generation. Our results demonstrate that in whole rat adrenal medulla, endothelins stimulate NO-induced cGMP generation through ET(B) receptors, and they support the concept that endothelins could play a role in the regulation of adrenal medulla function.