Cowpland Christine, Su Gloria M, Murray Michael, Puddey Ian B, Croft Kevin D
School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia.
Clin Exp Pharmacol Physiol. 2006 Mar;33(3):183-8. doi: 10.1111/j.1440-1681.2006.04337.x.
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 pro-hypertensive activity; CYP4A, by comparison, is the principal AA omega-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<0.001). The blood pressure of animals fed 5% alcohol in the form of red wine was not significantly different from controls over the study period. The urinary excretion of 20-HETE did not differ significantly among the treatment groups over the study period and there was no effect of any treatment on the metabolism of AA by renal microsomes. Red wine, but not administration of the relatively low dose of alcohol alone, increased the expression of CYP2E1 protein in the liver and kidney and CYP4A in the kidney. Both red wine and alcohol decreased CYP4A protein levels in the liver compared with controls. 4. Our results suggest that constituents of red wine, possibly polyphenols, can attenuate the alcohol-induced rise in blood pressure in the Sprague-Dawley rat, although this effect does not appear to be mediated by the inhibition of CYP-derived AA metabolism.
酒精性高血压已得到充分认识，多项人体干预研究提供了确凿证据，表明长期饮酒具有直接升压作用。在实验动物中，酒精对血压的影响不太一致；然而，在斯普拉格 - 道利大鼠中，给予酒精会持续引发高血压反应。酒精性高血压的机制尚不清楚。已知乙醇会诱导某些细胞色素P450（CYP）酶，特别是2E1同工型，该同工型已被证明可将花生四烯酸（AA）代谢为19 - 羟基代谢物（19 - HETE），而19 - HETE可能具有促高血压活性；相比之下，CYP4A是肝脏中主要的AAω - 羟化酶。多酚类化合物，如黄酮类化合物，已被证明可抑制某些CYP。2. 在本研究中，我们测定了给予酒精对大鼠血压和CYP依赖性AA代谢的影响，以及红酒多酚对其的可能调节作用。3. 将30只雄性斯普拉格 - 道利大鼠随机分为三组，分别给予水、低剂量乙醇（5% v/v）或红酒（稀释至含5%乙醇），持续9周。每周测量体重和血压，并在基线时以及每2周收集一次24小时尿液。9周后处死动物，收集血液和组织样本。与对照组相比，在研究期间给予酒精的大鼠血压显著升高（P<0.001）。在研究期间，以红酒形式给予5%酒精的动物血压与对照组无显著差异。在研究期间，各治疗组之间20 - HETE的尿排泄量无显著差异，且任何治疗对肾微粒体AA代谢均无影响。红酒，但单独给予相对低剂量的酒精则不会，可增加肝脏和肾脏中CYP2E1蛋白以及肾脏中CYP4A的表达。与对照组相比，红酒和酒精均可降低肝脏中CYP4A蛋白水平。4. 我们的结果表明，红酒成分，可能是多酚类物质，可减轻斯普拉格 - 道利大鼠中酒精诱导的血压升高，尽管这种作用似乎不是通过抑制CYP衍生的AA代谢介导的。
