Pharmacological analysis of 5-HT-induced vasoconstriction in isolated, perfused dog skeletal muscle arteries.
The mechanism of the vasoconstriction caused by 5-HT was analysed pharmacologically in isolated, perfused skeletal muscle branches of the canine femoral artery. An intraluminal injection of serotonin (5-HT) produced a marked vasoconstriction and the dose-response curve was bell-shaped. The 5-HT-induced response was inhibited by methysergide and ketanserin but a larger dose of ketanserin (10-30 micrograms) reduced the maximal responses to 5-HT, indicating its general depressant action. Norepinephrine (NE) and KCl-induced constrictions were not significantly affected by methysergide. Ketanserin significantly suppressed the NE-induced response at a relatively large dose but not the KCl-induced one. 5-HT- and KCl-induced constrictions were not modified by a potent alpha 1-adrenoceptor antagonist, bunazosin. It is considered that 5-HT may mediate its contractile effect on these arteries via specific 5-HT2 receptors but not alpha-adrenoceptors. Diltiazem at a relatively large dose (30-100 micrograms) slightly but significantly depressed NE-induced constrictions, and KCl-induced responses were markedly depressed by diltiazem (10-100 micrograms). On the other hand, 5-HT-induced constrictions were not suppressed by diltiazem at any of the doses used. It was shown that cold storage (at 4 degrees C, for 3-7 days) did not significantly modify 5-HT-induced responses although the KCl-induced effects were suppressed. Thus, it is considered that the calcium channel in these vessels may be dominantly depressed by cold storage. It is concluded that 5-HT-induced constriction in skeletal muscle arteries may be independent of the influx of extracellular Ca ions.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D003080:Cold Temperature; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D012701:Serotonin; D011189:Potassium Chloride; D007650:Ketanserin; C018176:bunazosin; D004110:Diltiazem; D009638:Norepinephrine; D008784:Methysergide