title: Vascular endothelial oxidative stress in alcohol-induced hypertension.
abstract: Epidemiological studies in humans and experimental studies in animals have shown the link between chronic alcohol consumption and the prevalence of hypertension. However, molecular mechanisms implicated with alcohol-induced increases in blood pressure (BP) remain elusive. The objective of this study was to investigate the relationship between BP and molecular as well as physiological changes in aortic endothelium in chronic ethanol treated rats. Male Fisher rats were given 20% ethanol (4 g/kg) orally and controls received 5% sucrose daily for 12 weeks. The BP was recorded weekly by tail-cuff method and after 12 weeks, rats were anesthetized with pentobarbital, thoracic aorta isolated and used for aortic reactivity using tissue bath and for biochemical analysis. The data show that ethanol ingestion significantly increased systolic, diastolic and mean BP after 12 weeks compared to control. The endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expressions were down-regulated leading to depletion of aortic NO levels in ethanol treated rats compared to control. The aortic NADPH oxidase activity significantly enhanced with a concomitant increase in membrane lipid peroxidation and depressed ratio of reduced to oxidized glutathione in alcohol-treated rats compared to control. The aortic vasoconstriction was slightly enhanced in response to phenylephrine but vasorelaxation was significantly diminished in response to acetylcholine, adenosine and sodium nitroprusside in chronic ethanol treated rats. It is concluded that chronic ethanol ingestion induces aortic endothelial oxidative injury and the down regulation of nitric oxide generating system leading to impaired vasorelaxation and hypertension in rats.
authors.affiliation: Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, Puerto Rico 00732, USA. khusain@psm.edu
authors.forename: K
authors.initials: K
authors.lastname: Husain
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000428:Alcohol Drinking; D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress; D010656:Phenylephrine / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D000431:Ethanol; D052250:Nitric Oxide Synthase Type III; D000241:Adenosine; D000109:Acetylcholine