Mediation by nitric oxide of the stimulatory effects of ethanol on blood flow.
The contribution of nitric oxide (NO) to the hemodynamic effects associated with alcohol oxidation was assessed in rats given either ethanol or water by gastric tube, with and without pre-treatment with either the NO synthase inhibitor N(omega)-monomethyl-L-arginine (L-NMMA; 15 mg/Kg i.p.) or the alcohol dehydrogenase inhibitor 4-methylpyrazole (4-MP; 82 mg/Kg i.p.). Alcohol increased plasma NO (measured with chemiluminescence) by 63%. This was prevented by either L-NMMA or 4-MP. Cardiac output and regional blood flows were determined with 57Cobalt-labeled microspheres. Alcohol markedly enhanced portal blood flow (130 +/- 6 ml/min/Kg vs. 62 +/- 4, in controls; p < 0.01) with no changes in the hepatic, splenic or pancreatic arterial blood flows, indicating that the vasodilatation is mainly mesenteric. In addition, it quadrupled the coronary blood flow, doubled the renal flow and increased cardiac output by 38%, with no significant changes in pulmonary, cerebral or testicular flows. All the stimulatory effects of ethanol on flow, as well as the rise in NO levels, were prevented by L-NMMA, incriminating NO as the mediator of the hemodynamic effects of ethanol oxidation, acting probably via acetate and adenosine.
Sections of Liver Disease and Nutrition, Alcohol Research Center, Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Enrique
E
Baraona
Lilia
L
Shoichet
Khursheed
K
Navder
Charles S
CS
Lieber
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D000077604:Fomepizole; D006321:Heart / Q000502:physiology*; D006801:Humans; D008297:Male; D008863:Microspheres; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D011168:Portal System / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012079:Renal Circulation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000431:Ethanol; D000077604:Fomepizole