Does EDRF/NO regulate its own release by increasing endothelial cyclic GMP?
EDRF/NO released from bovine aortic endothelial cells was measured by transferring conditioned medium to rat fetal lung fibroblasts (RFL-6 cells). These cells contain considerable amounts of soluble guanylyl cyclase. The increase in cyclic GMP in these cells provided a sensitive bioassay for EDRF/NO activity. Bovine aortic endothelial cells released a material that markedly enhanced cyclic GMP in RFL-6 cells. The synthesis of this substance could be stimulated with bradykinin (10 nM) or Ca2+ ionophore A23187 (1 microM) and was completely prevented by treatment of the endothelial cells with the EDRF/NO synthesis inhibitor, NG-L-arginine (100 microM), or incubation of the RFL-6 detector cells with the inhibitor of soluble guanylyl cyclase, methylene blue (10 microM). The release of EDRF/NO by bradykinin and A23187 was accompanied by an about two-fold increase in the cyclic GMP content in the producing endothelial cells. Incubation of bovine aortic endothelial cells with atrial natriuretic peptide (0.1 microM) or sodium nitroprusside (10 microM) enhanced their cyclic GMP content 6.5-fold and 4.1-fold, respectively. These increases in endothelial cyclic GMP levels had no effect on basal or bradykinin- and A23187-stimulated release of EDRF/NO. We conclude that cyclic GMP does not feed back on EDRF/NO formation or release in bovine aortic endothelial cells.
Kuhn
M
M
Department of Clinical Pharmacology, Hannover Medical School, FRG.
Förstermann
U
U
D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005246:Feedback; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats
D009569:Nitric Oxide; D006152:Cyclic GMP