Ethanol-induced contraction of cerebral arteries in diverse mammals and its mechanism of action.
Acute ethanol exposure (8-570 mM) induced potent contractile responses of rings in both basilar and middle cerebral arteries, from dogs, sheep, piglets and baboons, in a dose-dependent manner. The contractions were reproducible and not tachyphylactic. The middle cerebral arteries were found to be more sensitive to ethanol than the basilar arteries. No known pharmacological antagonist, tested, exerted any effects on ethanol-induced contractions. No differences in responsiveness to ethanol in canine cerebral arteries were found between male and female animals or between the presence and the absence of endothelial cells. Removal of extracellular Ca2+ ([Ca2+]o) partially attenuated ethanol-induced contractions, while withdrawal of extracellular Mg2+ ([Mg2+]o) potentiated such contractions. In the complete absence of [Ca2+]o, caffeine and ethanol induced similar, transient contractions followed by relaxation in K(+)-depolarized cerebral vascular tissue. Ethanol-induced contractions were completely abolished by pretreatment of tissues with caffeine. Our results suggest that: (a) acute ethanol intoxication can induce direct contractions (independent of amine, prostanoid or opioid mediation) of diverse mammalian cerebral vascular tissues, including those from primates; (b) these contractile responses are heterogeneous along the cerebrovascular tree and independent of endothelial cells; (c) in addition to a need for [Ca2+]o, an intracellular release of Ca2+ is needed for ethanol to induce contractions; and (d) hypomagnesemia or Mg deficiency potentiates the contractile effects of ethanol on brain vessels and may be a risk factor for ethanol-related, ischemic stroke events.
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Department of Physiology, State University of New York, Health Science Center at Brooklyn 11203.
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D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010215:Papio; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012756:Sheep; D013045:Species Specificity; D013552:Swine
D012701:Serotonin; D002110:Caffeine; D000431:Ethanol; D015237:Dinoprost; D008274:Magnesium; D011188:Potassium; D002118:Calcium