Heterogeneity of α1-Adrenoceptor Subtypes Mediating Noradrenaline-Induced Contractions of theRat Superior Mesenteric Artery

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Abstract
The effects of subtype-selective α1-adrenoceptor antagonists on noradrenaline-induced contractions of ring segments of rat superior mesenteric artery were investigated to determine the subtype(s) of α1-adrenoceptors mediating contractions in this preparation. Noradrenaline-induced contractions of rat mesenteric artery ring segments were potently and surmountably antagonized by prazosin, WB 4101 and BMY 7378. Judging from the slopes of the Schild regression lines, which were significantly different from 1, WB 4101 and BMY 7378 behaved as noncompetitive antagonists. Spiperone and 5-methylurapidil were only effective at high concentrations. Chloroethylclonidine (CEC, 100 µmol/l) displaced the noradrenaline concentration-response curve to the right reducing its potency approximately 100-fold. Noradrenaline-induced contractions post-CEC were also antagonized by prazosin. However, prazosin was less potent against these contractions. A 61603, a selective α1A-adrenoceptor agonist, contracted ring segments of the mesenteric artery. These contractions were antagonized by prazosin, however with a low affinity, indicating interaction with a low-affinity receptor subtype. It was therefore concluded that α1D- and, possibly, α1L-adrenoceptor subtypes mediated noradrenaline- induced contractions of the rat superior mesenteric artery.