RELAXATION OF RABBIT MIDDLE CEREBRAL ARTERIES IN VITRO BY H1 HISTAMINERGIC AGONISTS IS INHIBITED BY INDOMETHACIN AND TRANYLCYPROMINE

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Abstract
Summary— The H1‐histaminergic agonists 2‐pyridylethylamine (2‐PEA) and 2‐methylhistamine relaxed potassium‐constricted, perfused, rabbit middle cerebral arteries at low concentrations (3times10−11 to 3 times 10−8M) and constricted them at high concentrations (3 times 10−7 to 3 times 10−4M). The relaxation and the contraction were not antagonized by propranolol (up to 3times 10−6M) given 30 min before, suggesting that beta‐adrenergic mechanisms were not involved. When 2‐PEA was tested on arteries constricted with uridine triphosphate (UTP), similar results were obtained. In the UTP‐constricted arteries, the 2‐PEA‐induced responses were competitively antagonized by 3times 10−9M mepyramine. Together with previous work (Ea Kim et al., 1986), these results are compatible with the hypothesis that H1‐receptors were responsible for both the relaxation and the contraction observed.When either indomethacin (10−8, 3times 10−7, or 10−5M), dexamethasone (10−5M), or tranylcypromine (10−5 or 10−4M) were tested on the response to 2‐PEA or 2‐methylhistamine, these inhibitors suppressed the relaxation or reversed it to a contraction. Furthermore, they potentiated the contraction induced by these agonists. These results favour the hypothesis that the H1‐mediated relaxation in rabbit cerebral arteries may in part involve the release of prostaglandins, especially prostacyclin. The participation of such a prostanoid in histaminergic relaxation seems exclusively an H1‐mediated mechanism, since the relaxation induced by the H2‐agonist dimaprit (in the presence of mepyramine) was not antagonized by either indomethacin (3times 10−7M) or tranylcypromine (10−4M).