Glyceryl trinitrate increases platelet cyclic GMP after metabolism in fibroblasts.
Glyceryl trinitrate had no direct effect on cyclic GMP levels in platelets. However, in the presence of fibroblasts (RFL-6 cells), glyceryl trinitrate increased platelet cyclic GMP up to 7.8 fold (11.5 fold in the presence of superoxide dismutase). Fibroblasts alone had no effect. Endothelial cells alone increased platelet cyclic GMP up to 4.1 fold (9.6 fold in the presence of superoxide dismutase), but glyceryl trinitrate had no additional effect. Thus fibroblasts, but not endothelial cells, metabolize glyceryl trinitrate to a nitric oxide-like material that stimulates platelet soluble guanylyl cyclase.
Department of Clinical Pharmacology, Hannover Medical School, F.R.G.
M
M
Kuhn
A
A
Otten
J C
JC
Frölich
U
U
Förstermann
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D011863:Radioimmunoassay; D013482:Superoxide Dismutase / Q000494:pharmacology
D009569:Nitric Oxide; D013482:Superoxide Dismutase; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP