EFFECT OF ALCOHOL ON CYTOCHROME P450 ARACHIDONIC ACID METABOLISM AND BLOOD PRESSURE IN RATS AND ITS MODULATION BY RED WINE POLYPHENOLICS

SUMMARY 1 Alcohol‐induced hypertension is well recognized with clear evidence for a direct pressor effect of chronic alcohol consumption provided by a number of intervention studies in humans. In experimental animals, the effect of alcohol on blood pressure is less consistent; however, in Sprague‐Dawley rats, alcohol feeding consistently induces a hypertensive response. The mechanism of alcohol‐induced hypertension is not clearly understood. Ethanol is known to induce certain cytochrome P450 (CYP) enzymes, particularly the 2E1 isoform, which has been shown to metabolise arachidonic acid (AA) to the 19‐hydroxy metabolite (19‐HETE), which could have prohypertensive activity; CYP4A, by comparison, is the principal AA ω‐hydroxylase in the liver. Polyphenolic compounds, such as flavonoids, have been shown to inhibit some CYPs. 2 In this study, we determined the effect of alcohol administration on blood pressure and CYP‐dependent AA metabolism in the rat and its possible modulation by red wine polyphenols. 3 Thirty male Sprague‐Dawley rats were randomly allocated to three groups, which received water, low‐dose ethanol (5% v/v) or red wine (diluted to contain 5% ethanol) for a period of 9 weeks. Bodyweight and blood pressure were measured weekly and 24h urine collected at baseline and every 2 weeks. Animals were killed at 9 weeks and blood and tissue samples were collected. The blood pressure of rats fed with alcohol increased significantly over the period of the study compared with controls (P