Antioxidants prevent ethanol-induced contractions of canine cerebral vascular smooth muscle: relation to alcohol-induced brain injury.
The present study was designed to test the hypothesis that alpha-tocopherol (Vit. E) and pyrrolidine dithiocarbamate (PDTC) might exert direct effects on alcohol-induced contractions of canine basilar cerebral arteries. After precontraction of arterial ring segments with ethanol, PDTC (10(-8)-10(-6) M) and Vit. E (10(-6)-10(-4) M) induced concentration-dependent relaxations of cerebral arteries, compared to untreated controls. The effective concentrations producing approximately 50% of the maximal relaxation responses (EC(50) values) were about 2.48+/-0.09 x 10(-7) M for PDTC, and 1.87+/-0.10 x 10(-5) mM for Vit. E, respectively. Preincubation of these arterial rings with EC(50)'s of PDTC or Vit. E for 40 min attenuate markedly the contractions produced by alcohol, at concentrations of 1-400 mM. However, both PDTC and Vit.E do not relax equi-potent precontractions induced by either KCl or prostaglandin F(2alpha) (PGF(2alpha)) or inhibit their contractions. These data suggest that alcohol-induced contractions of cerebral arteries are mediated via excitation-contraction coupling pathways different from those used by KCl or receptor-mediated agonists such as PGF(2alpha). The present results, when viewed in light of other recently published data, suggest that antioxidants may prove useful in the amelioration and treatment of alcohol-induced brain damage and strokes.
Department of Physiology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply; D002118:Calcium / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D020521:Stroke / Q000139:chemically induced / Q000188:drug therapy; D013859:Thiocarbamates / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D002492:Central Nervous System Depressants; D011759:Pyrrolidines; D013859:Thiocarbamates; D014810:Vitamin E; C020972:pyrrolidine dithiocarbamic acid; D000431:Ethanol; D011189:Potassium Chloride; D015237:Dinoprost; D008274:Magnesium; D002118:Calcium