Dose response of alcohol-induced changes in BP, nitric oxide and antioxidants in rat plasma.
Moderate ethanol consumption is known to reduce the risk of cardiovascular diseases; however, chronic high dose ethanol ingestion causes cardiovascular injuries including hypertension. The dose response of ethanol-induced hypertension and associated oxidative stress response has not been well established. This study investigated the dose response of ethanol on blood pressure (BP), nitric oxide (NO) and antioxidants in the plasma of the rat. Male Fisher rats (200-250 g) were divided into five groups of six animals each and treated as follows: (1) control (5% sucrose, orally) daily for 12 weeks; (2) 20-30% ethanol (1 g kg-1, orally) daily for 12 weeks; (3) 20-30% ethanol (2 g kg-1, orally) daily for 12 weeks; (4) 20-30% ethanol (4 g kg-1, orally) daily for 12 weeks; (5) 20-30% ethanol (6 g kg-1, orally) daily for 12 weeks. The BP (systolic, diastolic and mean) was recorded every week through tail-cuff method. The animals were sacrificed 12 weeks after treatments and blood was collected and analyzed. Systolic and mean BP were slightly decreased with 1 g kg-1 dose but significantly elevated with 2, 4 and 6 g kg-1 doses 7-12 weeks after ethanol ingestion. Whereas diastolic BP was significantly elevated with 4 and 6 g kg-1 doses 8-12 weeks after ethanol ingestion. Blood alcohol levels were significantly elevated with 4 and 6 g kg-1 dose of ethanol for 12 weeks. Ethanol dose-dependency increased plasma malondialdehyde (MDA) and protein carbonyl levels, while nitric oxide (NO), ratio of reduced to oxidized glutathione (GSH/GSSG) and antioxidant enzymes: copper/zinc-superoxide dismutase (CuZn-SOD) and manganese (Mn)-SOD, catalase (CAT) and glutathione peroxidase (GSH-Px) activities were decreased 12 weeks post-treatment. The data suggested that ethanol induces hypertension at higher doses by depleting NO and antioxidants and increasing oxidative tissue injury in rats.
Husain
Kazim
K
Department of Pharmacology and Toxicology, Ponce School of Medicine, P.O. Box 7004, Ponce, PR 00732, USA. khusain@psm.edu
Mejia
Jose
J
Lalla
Jainarine
J
Kazim
Sheeba
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D051381:Rats; D011916:Rats, Inbred F344
D000975:Antioxidants; D009569:Nitric Oxide; D000431:Ethanol