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The cytochrome p450 (CYP) superfamily is responsible for the oxidation, peroxidation, and (or) reduction of vitamins, steroids, xenobiotics, and the majority of cardiovascular drugs in an oxygen- and NADPH-dependent manner. Although hepatic CYP have been studied extensively, the role of CYP in cardiovascular physiology and disease is poorly understood. Increasing evidence suggests that these enzymes play an important role in the pathogenesis of a number of cardiovascular diseases. The current review summarizes the understanding as to the role that dysregulated CYP expression and (or) activity may play in the onset and progression of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: Vascular dysfunction is linked with increased free radical generation and is a major contributor to the high mortality rates observed in diabetes. Several probable sources of free radical generation have been suggested in diabetes, including cytochrome P450 (CYP) monooxygenase-dependent pathways. CYP-mediated superoxide production reduces nitric oxide (NO) bioavailability. In this study, we focus on the contribution of monooxygenase enzyme-generated reactive oxygen species in vascular dysfunction in an experimental model of diabetes mellitus type II. Diabetic male mice (db/db strain) and their age-matched controls received daily intraperitoneal injections of either the CYP 2C inhibitor sulfaphenazole (5.13 mg/kg) or saline (vehicle control) for 8 weeks. Although sulfaphenazole did not change endothelium-dependent vasodilation in control mice, it restored endothelium-mediated relaxation in db/db mice. We report for the first time that CYP 2C inhibition reduces oxidative stress (measured as plasma levels of 8-isoprostane), increases NO bioavailability (measured as NO2 −) and restores endothelial function in db/db mice without affecting plasma glucose levels. Based on our findings, we speculate that inhibition of free radical generating CYP 450 monooxygenase enzymes restores endothelium-dependent vasodilation to acetylcholine. In addition, it reduces oxidative stress and increases NO bioavailability. [Copyright &y& Elsevier]