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

Article Details

Citation

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

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

Proc Soc Exp Biol Med. 1995 May;209(1):60-4.

PubMed ID
7536941 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MiconazoleNitric oxide synthase, endothelialProteinHumans
Unknown
Inhibitor
Details
MiconazoleNitric oxide synthase, inducibleProteinHumans
Unknown
Inhibitor
Details