Mechanism underlying responses to histamine of isolated monkey and human cerebral arteries.
Cerebral artery strips obtained from Japanese monkeys partially contracted with prostaglandin F2 alpha responded to histamine with a relaxation that was attenuated by treatment with cimetidine or chlorpheniramine and was abolished by their combined treatment. Endothelium denudation suppressed the relaxation; the remaining relaxation was not influenced by the H1 antagonism but was abolished by the H2 antagonism. Treatment with methylene blue slowed the development of relaxation and, in the presence of cimetidine, depressed the magnitude of relaxation. Indomethacin did not alter the response. In the main trunk of human middle cerebral arteries obtained during autopsy, histamine predominantly caused contractions, whereas third and fifth branches responded exclusively with a dose-dependent relaxation. The contraction was abolished by chlorpheniramine, and the relaxation was attenuated by either chlorpheniramine or cimetidine. Removal of endothelium suppressed or reversed the relaxation to a contraction. It appears that the histamine-induced relaxation is mediated by endothelial H1 receptors responsible for the release of endothelium-derived relaxing factor and also by H2 receptors in smooth muscle, whereas the contraction is associated with activation of smooth muscle H1 receptors. Involvement of the receptor subtypes in the observed response of monkey and human cerebral arteries quantitatively differs. Physiological and pathophysiological roles of endogenous histamine acting on the large cerebral arteries may be postulated.
Toda
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Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
D000818:Animals; D001696:Biomechanical Phenomena; D000001:Calcimycin / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008251:Macaca / Q000502:physiology*; D008751:Methylene Blue / Q000494:pharmacology; D009994:Osmolar Concentration; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation
D000001:Calcimycin; D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D008751:Methylene Blue