Alcohol suppresses endothelium-dependent relaxation in rat mesenteric vascular beds.
The effects of prolonged infusions of ethanol on endothelium-dependent vasorelaxation induced by acetylcholine and adenosine triphosphate (ATP) and on endothelium-independent relaxation induced by papaverine were studied and compared in isolated perfused rat mesenteric artery preparations. Infusion of ethanol over 60 minutes at concentrations of 1.6, 4.7, 6.3, and 7.9 mg/ml caused concentration-related inhibition of norepinephrine-induced vasoconstriction. In preparations infused with 6.3 and 7.9 mg/ml, this effect reached a maximum after 10-20 minutes but had vanished by the end of the infusion; 1 hour after the end of the infusion, the effects of norepinephrine were potentiated by 71% and 108%, respectively. Acetylcholine-induced vasorelaxation (EC50 3.0 ng/ml in controls) was significantly reduced after 6.3 mg/ml ethanol infusion and totally abolished after 7.9 mg/ml ethanol infusion. ATP-induced vasorelaxation (EC50 180 ng/ml in controls) was also abolished after 7.9 mg/ml of ethanol infusion. By contrast, the vasorelaxant effects of papaverine were not affected by 7.9 mg/ml ethanol infusion. Light-microscopic examination revealed that the endothelial cells were present in ethanol-treated and in control mesenteric arterial beds. These observations indicate that ethanol suppresses endothelium-dependent vasorelaxation without apparent removal of the endothelial cells. The compromised relaxant capacity of the endothelium after ethanol and the resultant intensification of the vasoconstrictor response to norepinephrine may contribute to the development of vascular diseases such as hypertension and stroke.
Criscione
L
L
Cardiovascular Research Department, CIBA-GEIGY Ltd., Basel, Switzerland.
Powell
J R
JR
Burdet
R
R
Engesser
S
S
Schlager
F
F
Schoepfer
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004730:Endothelium, Vascular; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation
D001685:Biological Factors; D009569:Nitric Oxide; D000431:Ethanol; D000255:Adenosine Triphosphate; D010208:Papaverine; D000109:Acetylcholine; D009638:Norepinephrine