Heterogeneity of alpha 1-adrenoceptor subtypes mediating noradrenaline-induced contractions of the rat superior mesenteric artery.

The effects of subtype-selective alpha 1-adrenoceptor antagonists on noradrenaline-induced contractions of ring segments of rat superior mesenteric artery were investigated to determine the subtype(s) of alpha 1-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 mumol/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 61,603, a selective alpha 1A-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 alpha 1D- and, possibly, alpha 1L-adrenoceptor subtypes mediated noradrenaline- induced contractions of the rat superior mesenteric artery.