Pharmacological characterization of alpha-adrenoreceptor subtypes in rat isolated thoracic aorta.

The subtype of alpha-adrenoreceptor mediating contraction in rat isolated thoracic aorta was classified pharmacologically using preferential agonists and antagonists, and by utilizing mixed agonist and antagonist interactions. Noradrenaline was 8 to 10-times more potent at contracting the aorta than phenylephrine and both agonists were about 1000 and 10,000-fold respectively more potent than azepexole (a preferential alpha 2-agonist). Prazosin (a preferential alpha 1-antagonist) inhibited the dose-response curves to noradrenaline and phenylephrine 100 and 1000-times respectively more effectively than either phentolamine or rauwolscine (a preferential alpha 2-antagonist). Furthermore, prazosin (5 x 10(-9) M) completely abolished contractions elicited by a single concentration of azepexole (3 x 10(-4) M). In mixed antagonist studies, rauwolscine (5 x 10(-7) M) failed to shift the dose-response curves to noradrenaline and phenylephrine obtained in the presence of prazosin (5 x 10(-9) M). In mixed agonist experiments, azepexole (3 x 10(-4) M) acted as a partial antagonist toward phenylephrine-induced contractions. The results suggest that the alpha-adrenoreceptor of the rat thoracic aorta is predominantly, if not exclusively, of the alpha 1-subtype.