Endothelial thromboxane production plays a role in the contraction caused by 5-hydroxytryptamine in rat basilar arteries.
The goal of the present study was to characterize the role of the endothelium in the 5-hydroxytryptamine (5-HT)-induced contraction of the rat basilar artery. Rat basilar artery segments were mounted in myographs to study their isometric tension development. 5-HT caused dose-dependent contractions that were minimally affected by endothelium removal. The dose-response curve obtained with the 5-HT1 receptor agonist, 5-carboxamidotryptamine (5-CT), was biphasic in arteries with endothelium; removal of the endothelium eliminated the first phase of the contraction. The 5-HT2 receptor antagonist, ketanserin (30 nM), shifted the dose-response curve to 5-HT to the right; in arteries with endothelium, the curve became biphasic. Ketanserin inhibited the second phase of the dose-response curve to 5-CT. The mixed 5-HT1/5-HT2 receptor antagonist, metergoline (30 nM), shifted the dose-response curve to 5-HT non-competitively to the right and depressed both phases of the dose-response curve to 5-CT. In basilar arteries with endothelium and treated with ketanserin, the thromboxane A2 receptor antagonist, ICI 192605 (1 microM), significantly decreased the responsiveness to 5-HT and the dose-response curve for 5-HT became monophasic. ICI 192605 and the thromboxane A2 synthase inhibitor, ridogrel (10 microM), both suppressed the first phase of the dose-response curve to 5-CT. These data indicate that both endothelial 5-HT1 and smooth muscle 5-HT2 receptors participate in the contractions caused by 5-HT in the rat basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Descombes
J J
JJ
Division of Angiology, Institut de Recherche Servier, Suresnes, France.
Devys
M
M
Laubie
M
M
Verbeuren
T J
TJ
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010421:Pentanoic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000096:biosynthesis / Q000502:physiology*
D004146:Dioxanes; D010421:Pentanoic Acids; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013931:Thromboxanes; C057498:ICI 192605; D008711:Metergoline; D012701:Serotonin; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D013930:Thromboxane-A Synthase; C060219:ridogrel