title: Down-regulation of ventricular nitric oxide generating system in chronic alcohol-treated hypertensive rats.
abstract: Epidemiological studies show that low to moderate doses of alcohol consumption is beneficial to cardiac health. However, chronic high doses of alcohol ingestion cause cardiovascular complications including hypertension. The molecular and cellular mechanisms of chronic ethanol-induced increase in blood pressure (BP) are not completely understood. The purpose of this study was to investigate whether the increase in blood pressure following chronic ethanol exposure relates to cardiac endothelial nitric oxide levels and its generating system. Male Fisher rats were given 20% ethanol (4 g/kg, orally) through orogastric tube daily for 12 weeks and controls received 5% sucrose through orogastric tube daily for 12 weeks. The systolic, diastolic and mean BP was recorded through tail-cuff method. After 12 weeks, rats were sacrificed and heart dissected and left ventricle isolated and analyzed using enzyme linked immunosorbant assay (ELISA) and Western blotting. Results show that ethanol ingestion caused a significant increase in systolic, diastolic and mean BP (p<0.001) compared to control after 12 weeks. The levels of nitric oxide, its generating enzyme endothelial nitric oxide synthase (eNOS) protein expression and vascular endothelial growth factor (VEGF) gene (mRNA) and protein expressions were significantly down-regulated in the endothelium of left ventricles of ethanol-treated rats compared to controls. It is concluded that chronic ethanol ingestion causes an increase in blood pressure in rats via endothelial oxidative injury and the down-regulation of nitric oxide generating system in the left ventricles.
authors.affiliation: Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, Puerto Rico. khusain@psm.edu
authors.forename: K
authors.initials: K
authors.lastname: Husain
authors.forename: M
authors.initials: M
authors.lastname: Vazquez-Ortiz
authors.forename: J
authors.initials: J
authors.lastname: Lalla
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; D000431:Ethanol; D052250:Nitric Oxide Synthase Type III