Further characterization of antagonism by alpha(2)-adrenoceptor agonists of contractions induced by alpha(1)-adrenoceptor agonists

The population of alpha(2)-adrenoceptor subtypes functionally mediating contraction in response to phenylephrine was examined in rat thoracic aorta and tail arteries. In thoracic aorta, chloroethylclonidine (CEC), which alkylates the alpha(1B) and alpha(1D) subtypes, shifted the concentration-response curve for phenylephrine substantially to the right without reduction in maximum contraction. The pA(2) value (7.8) for 5-methylurapidil was consistent with the values reported for alpha(1D) subtype, but was higher than those in tissues in which the alpha(1B) subtype is dominant. In tail arteries, CEC did not shift the concentration-response curve for phenylephrine, but somewhat inhibited the maximum contraction. Schild analysis for 5-methylurapidil yielded a straight line with a slope significantly less than unity. Prazosin antagonized phenylephrine-induced contraction of tail arteries in a competitive manner with a pA(2) value of 8.5, consistent with values for alpha(1L) subtype. Clonidine relaxed the active tone induced by phenylephrine in both thoracic aorta and tail arteries, but quite different responses to clonidine by the two tissues were observed. After pretreatment with CEC, the relaxation induced by clonidine was abolished in thoracic aorta, but not in tail arteries. These results suggest that alpha(1D)-and alpha(1L)-adrenoceptors are mainly present in thoracic aorta and tail arteries, respectively. This difference in the populations of alpha(1)-adrenoceptor subtypes may be related to regional differences in the modes of relaxant action of clonidine.