Influence of the endothelium on contractile effects of 5-hydroxytryptamine and selective 5-HT agonists in canine basilar artery.
1. We have investigated the influence of endothelial damage on the cerebrovascular reactivity to 5-hydroxytryptamine (5-HT) and some selective 5-HT agonists in canine basilar artery. 2. 5-HT, alpha-methyl 5-HT, GR 43175 (3-[2-dimethyl amino] ethyl-N-methyl-1H-indole-5-methane sulphonamide) and 5-carboxamidotryptamine (5-CT) produced concentration-dependent contractions of untreated dog basilar artery with a functional endothelium. Following endothelial damage by perfusion with Triton X-100 (0.1%), which abolished the relaxant response to substance P, the maximum contractile effect of 5-HT, alpha-methyl 5-HT, GR 43175 and 5-CT was markedly enhanced although there was little change in the EC50 values. Endothelial damage did not modify the vasoconstrictor effect of the thromboxane agonist, U46619, or potassium chloride. 3. Neither 5-HT nor 5-CT caused relaxation of untreated canine basilar arteries contracted with prostaglandin F2 alpha, U46619, uridine triphosphate or potassium chloride. 4. These results suggest that canine basilar artery spontaneously releases endothelium-derived relaxing factor which can attenuate the vasoconstrictor effect of 5-HT and selective 5-HT agonists. This effect appeared to be specific since the vasoconstrictor response to U46619 was not modified. 5. These results demonstrate that the cerebrovascular endothelium can markedly influence the reactivity of the vascular smooth muscle of canine basilar artery to 5-HT and 5-HT1-like receptor agonists. However we could find no evidence that 5-HT receptor activation stimulates endothelial cell function as it does in some other blood vessels.
Connor
H E
HE
Department of Cardiovascular Pharmacology, Glaxo Group Research, Ware, Herts.
Feniuk
W
W
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D003902:Detergents / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan
D003902:Detergents; D007211:Indoles; D012702:Serotonin Antagonists; D013449:Sulfonamides; C042390:alpha-methylserotonin; D012701:Serotonin; D011092:Polyethylene Glycols; D008719:Methiothepin; D011189:Potassium Chloride; D018170:Sumatriptan; D017830:Octoxynol; C047087:5-carboxamidotryptamine; D007650:Ketanserin