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 less than 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 less than 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.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008751:Methylene Blue / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000378:metabolism*
D001095:Arachidonic Acids; D009599:Nitroprusside; D016718:Arachidonic Acid; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D012083:Renin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D007545:Isoproterenol; D008751:Methylene Blue