The effects of denopamine, clinically used as a cardiotonic beta(1)-adrenoceptor agonist, were investigated on alpha-adrenoceptor-mediated contraction in vascular preparations of rats, guinea-pigs and rabbits. Norepinephrine, phenylephrine (alpha(1)-adrenoceptor agonist) and clonidine [and 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK 14,304, alpha(2)-adrenoceptor agonists)] concentration dependently contracted the vascular preparations. Phenylephrine was more potent than the alpha(2)-adrenoceptor agonists in the rat aorta and carotid artery. The reverse was true in the rabbit ear vein, pA(2) values for prazosin (rat tissues, 9.7-10; guinea-pig aorta, 9.1-9.3) and for yohimbine (rat tissues, 6.6-6.9; guinea-pig aorta, 6.2-6.3; rabbit ear vein, 7.9) suggested that alpha(1H) (high affinity for prazosin)-, alpha(1L) (lower affinity for prazosin)-, and alpha(1H)-adrenoceptors were predominantly distributed in the rat tissues, the guinea-pig aorta, and in the rabbit ear vein, respectively. Vasoconstrictions mediated by alpha(1H)-adrenoceptor subtypes were more susceptible to inhibition by denopamine than those mediated by alpha(1L) and alpha(2) subtypes. These results suggested that in addition to activity as a beta(1)-adrenoceptor agonist, denopamine also possessed activity as an alpha(1H)-adrenoceptor-selective antagonist. These actions may contribute to the denopamine-induced decrease in total peripheral resistance in vivo.
