QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.127498v1 324/1/368    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by El-Mas, M. M. Articles by Abdel-Rahman, A. A. Search for Related Content PubMed PubMed Citation Articles by El-Mas, M. M. Articles by Abdel-Rahman, A. A.

CARDIOVASCULAR

Endotoxemia-Mediated Induction of Cardiac Inducible Nitric-Oxide Synthase Expression Accounts for the Hypotensive Effect of Ethanol in Female Rats

Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina

We have recently shown that intragastric (i.g.) ethanol lowers blood pressure (BP) in conscious female rats via a reduction in cardiac output (CO). However, the mechanisms implicated in these hemodynamic effects of ethanol are not known. Therefore, we tested the hypothesis that ethanol-evoked endotoxemia mediates the reduction in CO via enhanced myocardial inducible nitric-oxide synthase (iNOS) expression. Immunoblot (myocardial iNOS), biochemical (plasma endotoxin and nitrite/nitrate), and integrative [BP, heart rate, CO, stroke volume (SV), and total peripheral resistance (TPR)] studies were conducted in conscious female rats that received i.g. ethanol (1 g/kg) in the absence or presence of 1400W (N-(3-[aminomethyl]benzyl) acetamidine) or ampicillin to selectively inhibit iNOS and to eliminate endogenous endotoxin, respectively. Ethanol-evoked hypotension coincided with reductions in CO and SV and increases in: 1) TPR, 2) plasma endotoxin and nitrite/nitrate, and 3) myocardial iNOS expression. These effects of ethanol were virtually abolished in rats pretreated with ampicillin (200 mg/kg/day for 2 days by gavage) or with 1400W (5 mg/kg i.p.) except for the increase in plasma endotoxin, which persisted in 1400W-pretreated rats. These findings yield insight into the mechanistic role of endotoxin-myocardial iNOS signaling in the cardiodepressant action of ethanol, which accounts for its hypotensive effect in conscious female rats.