Inhibition of endothelial nitric oxide synthase by cytochrome P-450 reductase inhibitors.

R R Dudek, A Conforto, V Pinto, S Wildhirt, H Suzuki

Department of Experimental Cardiology, Huntington Medical Research Institutes, Pasadena, California 91101, USA.

Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 1995 May

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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.

Citation

R R Dudek, A Conforto, V Pinto, S Wildhirt, H Suzuki. Inhibition of endothelial nitric oxide synthase by cytochrome P-450 reductase inhibitors. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.). 1995 May;209(1):60-4