Cytochrome P-450: a new target in the heart and coronary curculation

Cytochrome P-450 enzymes (CYPs) are present in the heart and coronary circulation. The activation of CYP2J2/3 to increase the production of epoxyeicosatrienoic acids (EETs) may be cardioprotective in cardiac ischemia and reperfusion. On the other hand, inhibition of CYP2C9 with cimetidine, or more selectively with sulfaphenazole, is cardioprotective in the perfused rat heart. In a dog model of cardiac ischemia and reperfusion, inhibitors of CYP co-hydroxylases (e.g., CYP4A, CYP4F) reduce infarct size. Inhibition of selected CYPs as an approach to the treatment of myocardial infarction should therefore be further developed. The function of CYPs in the coronary artery and other blood vessels is varied and complex, and only just beginning to be elucidated. In the coronary artery, when nitric oxide (NO) bioavailability is inhibited, the activity of CYPs may be increased, with the production of vasodilatory EETs. Conversely, when CYP2C9 is inactivated in humans with coronary artery disease (CAD), acetylcholine-induced NO-mediated vasodilatation is enhanced. In the presence of CAD/oxidized LDL, the EET vasodilator/system may be inhibited. Drugs that target CYPs and/or EETs are thus expected to be useful in the elucidation of the role of this system, and may also have therapeutic utility. Copyright