Denopamine as an alpha 1H-adrenoceptor antagonist in isolated blood vessels.

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. pA2 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 2-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.