Relaxation of rabbit middle cerebral arteries in vitro by H1 histaminergic agonists is inhibited by indomethacin and tranylcypromine.
The H1-histaminergic agonists 2-pyridylethylamine (2-PEA) and 2-methylhistamine relaxed potassium-constricted, perfused, rabbit middle cerebral arteries at low concentrations (3 x 10(-11) to 3 x 10(-8) M) and constricted them at high concentrations (3 x 10(-7) to 3 x 10(-4) M). The relaxation and the contraction were not antagonized by propranolol (up to 3 x 10(-6) M) 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 3 x 10(-9) M 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), 3 x 10(-7), or 10(-5) M), dexamethasone (10(-5) M), or tranylcypromine (10(-5) or 10(-4) M) 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 (3 x 10(-7) M) or tranylcypromine (10(-4) M).
Ea Kim
L
L
Laboratoire de Pharmacologie, U.E.R. de Médecine et Pharmacie, Limoges, France.
Sercombe
R
R
Oudart
N
N
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects*; D017259:Dimaprit; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008761:Methylhistamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011817:Rabbits; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects; D013890:Thiourea / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology*
D008761:Methylhistamines; D011725:Pyridines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D014191:Tranylcypromine; C006183:2-(2-aminoethyl)pyridine; D013890:Thiourea; D007213:Indomethacin; D017259:Dimaprit