Chronic ethanol ingestion increases aortic endothelial nitric oxide synthase expression and nitric oxide production in the rat.
BACKGROUND
Chronic alcohol consumption perturbs cellular function in a variety of organ systems. Previous studies have suggested that moderate alcohol consumption reduces vascular disease, whereas heavier alcohol consumption may worsen it. The mechanisms for these vascular effects of chronic alcohol ingestion continue to be defined and constitute the focus of this study.


METHODS
Male Sprague Dawley rats were fed an isocaloric, Lieber-Decarli liquid diet containing either ethanol (36% calories) or Maltose-Dextrin (substituted for ethanol) for 6 weeks. Telemetric blood pressure measurements were taken before and after ethanol feeding. After the rats were killed, the aortas were analyzed for endothelial nitric oxide (NO) synthase expression and NO production.


RESULTS
Chronic ethanol ingestion decreased mean arterial pressure and increased aortic NO production as demonstrated by direct ex vivo measurements using iron diethyldithio-carbamic acid as well as analysis of nitrosyl-hemoglobin (NO-Hb) levels. Consistent with these assays of vascular NO production, endothelium-dependent relaxation responses to acetycholine (Ach) were enhanced in ethanol-fed animals. Aortic endothelial nitric oxide synthase expression was also increased by chronic ethanol ingestion.


CONCLUSIONS
These findings demonstrate that a regimen of chronic alcohol ingestion in the rat produced generally salutary effects in the systemic vasculature following a 6-week treatment regimen. These findings extend previous in vitro studies to demonstrate that alcohol has potent effects on vascular endothelial nitric oxide synthase expression, NO production, and vascular function. Consistent with previous reports, these findings confirm that alcohol-induced alterations in the production of reactive nitrogen species play an important role in the pathogenesis of alcohol-mediated tissue effects.
Kleinhenz
Dean J
DJ
Department of Medicine, Atlanta Veterans Affairs and Emory University Medical Centers, Atlanta, Georgia 30033, USA.
Sutliff
Roy L
RL
Polikandriotis
John A
JA
Walp
Erik R
ER
Dikalov
Sergey I
SI
Guidot
David M
DM
Hart
C Michael
CM
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D042783:Endothelial Cells / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D009569:Nitric Oxide; D000431:Ethanol; D052250:Nitric Oxide Synthase Type III