A Randomized Trial of Effects of Alcohol on Cytochrome P450 Eicosanoids, Mediators of Inflammation Resolution, and Blood Pressure in Men

Anne E. Barden, Venus Chavez, Michael Phillips, Emilie Mas, Lawrence J. Beilin, Kevin D. Croft, Trevor A. Mori, Ian B. Puddey

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Abstract

Background: Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress, and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2-isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs), and specialized pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Methods: Normotensive men (n = 22) were randomly allocated to drink RW (375 ml/d) or the equivalent volume of dealcoholized red wine (DRW) or water for 4 weeks in a 12-week, 3-period crossover trial. BP, heart rate, 20-HETE, F2-isoprostanes, and SPM were measured at baseline, 4, 8, and 12 weeks. Results: Drinking RW increased BP (p < 0.05), plasma and urinary 20-HETE (p < 0.05), plasma F2-isoprostanes (p < 0.0001), and the SPMs 18-hydroxyeicosapentaenoic acid (18-HEPE) from EPA, and resolvin D1 (RvD1) and 17R-resolvin D1 (17R-RvD1) from DHA (all p < 0.05) compared with DRW and water. EETs and high-sensitivity C-reactive protein were unaffected by RW. Plasma 18-HEPE was positively related to urinary 20-HETE (p < 0.008) only after RW. Conclusions: This study has shown that men consuming moderate-to-high alcohol as RW for 4 weeks had increased BP, 20-HETE, and oxidative stress, as well as specific SPM that resolve inflammation. These paradoxical findings require further studies to determine whether alcohol stimulates different CYP450 enzymes and whether the findings can be replicated in females.

Original languageEnglish
Pages (from-to)1666-1674
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume41
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017

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