Inhibition of endothelial nitric oxide synthase by cytochrome P-450 reductase inhibitors.
Nitric oxide synthase (NOS) shows similarities to cytochrome P-450 reductase. The two enzymes catalyze the oxidation of N-omega-hydroxy-L-arginine by NADPH and oxygen to nitric oxide (NO) and citrulline. Nitric oxide synthase activity is inhibited by L-arginine analogs like N-omega-nitro-L-arginine, which does not affect cytochrome P-450 reductase. Dihydroergotamine, miconazole, and troleandomycin are classical inhibitors of cytochrome. The present study shows the concentration-dependent inhibitory effect of these compounds and of L- but not D-N-omega-nitro-arginine on the activity of constitutive nitric oxide synthase from bovine aortic endothelial cells. Activity of nitric oxide synthase was estimated by measurement of conversion of [3H]arginine to [3H]citrulline. The tested cytochrome P-450 inhibitors are likely to interfere with heme of nitric oxide synthase. The data confirms a similarity as well as functional differences between the enzymes.
Dudek
R R
RR
Department of Experimental Cardiology, Huntington Medical Research Institutes, Pasadena, California 91101, USA.
Conforto
A
A
Pinto
V
V
Wildhirt
S
S
Suzuki
H
H
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D004087:Dihydroergotamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D008825:Miconazole / Q000494:pharmacology; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D014217:Troleandomycin / Q000494:pharmacology
D019335:Nitroarginine; D004087:Dihydroergotamine; D008825:Miconazole; D001120:Arginine; D014217:Troleandomycin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase