Guanosine 3',5'-cyclic monophosphate as a mediator of inhibition of renin release

The role of guanosine 3',5'-cyclic monophosphate (cGMP) as an inhibitory mediator of tissue renin release was examined in two different in vitro preparations. In rat superficial cortical slices, renin release stimulated by isoproterenol (10^-5 M) was ablated by atriopeptin III (ANP, 2.1 x 10^-8 M), nitroprusside (NP, 10^-3 M), and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 10^-3 and 10^-6 M). Arachidonic acid (10^-3 M)-stimulated renin release was also inhibited by ANP and 8-BrcGMP (10^-3 and 10^-6 M). Both ANP and NP increased tissue cGMP concentrations significantly (P < 0.05), but neither had an effect on adenosine 3',5'-cyclic monophosphate (cAMP) concentrations. When methylene blue (10^-5 M), an inhibitor of guanylate cyclase, was added to slices incubated with isoproterenol and ANP, the inhibition of renin release by ANP was abolished. These results were confirmed in a preparation of isolated cultured rat juxtaglomerular cells. In these cells, isoproterenol induced a significant increase (58%, P < 0.01) in renin release, which was inhibited by the addition of 8-BrcGMP (10^-6 M). These data demonstrate a direct inhibitory effect of ANP on isoproterenol- and arachidonic acid-induced renin release. The results with NP, 8-BrcGMP, and methylene blue suggest that cGMP is an intracellular mediator of this inhibition.