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.