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1 5-Hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) stimulated additional, endothelium-dependent contractions in rabbit isolated basilar arteries which had been submaximally contracted with either histamine or potassium chloride. 2 The additional contractions to 5-HT were not altered by the 5-HT2 antagonist, ketanserin (1 microM), but were abolished in the presence of the cyclo-oxygenase inhibitor indomethacin (3 microM). 3 The additional smooth muscle contraction stimulated by 5-HT was increased in the presence of the competitive substrate inhibitor for nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). 4 Neither of the selective 5-HT agonists, 8-hydroxy-dipropylaminotetralin (8-OH DPAT) or alpha-methyl 5-HT stimulated endothelium-dependent contraction, but these agonists did reduce the rate at which histamine-induced tension spontaneously declined. This effect represented a direct action on the smooth muscle cells, as it was independent of the presence of endothelial cells. 5 Smooth muscle relaxation was not obtained in response to 5-HT, whether or not indomethacin was present to block endothelium-dependent contraction. None of the other selective 5-HT agonists, 5-CT, 8-OH DPAT or alpha-methyl 5-HT produced endothelium-dependent smooth muscle relaxation, when applied against a background of contraction. 6 These data show that endothelium-dependent smooth muscle contraction can be produced by stimulating 5-HT receptors in the partially contracted rabbit basilar artery. Similar contraction to 5-CT indicates an involvement by 5-HT1 receptors. The susceptibility of the contractions to indomethacin suggest they are mediated by a metabolite of arachidonic acid.

Type

Journal article

Journal

Br j pharmacol

Publication Date

02/1992

Volume

105

Pages

424 - 428

Keywords

8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Arginine, Basilar Artery, Endothelium, Vascular, Female, In Vitro Techniques, Indomethacin, Ketanserin, Male, Muscle Contraction, Muscle Relaxation, Muscle, Smooth, Vascular, NG-Nitroarginine Methyl Ester, Rabbits, Serotonin, Serotonin Antagonists, Tetrahydronaphthalenes