Endothelium-dependent contractile responses to 5-hydroxytryptamine in the rabbit basilar artery.
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.
Seager
J M
JM
Department of Physiology and Pharmacology, University of Southampton.
Clark
A H
AH
Garland
C J
CJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D011817:Rabbits; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C042390:alpha-methylserotonin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001120:Arginine; D007650:Ketanserin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin