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 (EC50 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 EC50'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 KCI or prostaglandin F-2u (PGF(2 alpha)) 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 KCI or receptor-mediated agonists such as PGF(2 alpha). 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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.