The cardiovascular actions of dopexamine hydrochloride, an agonist at dopamine receptors and β2-adrenoceptors in the dog

Abstract

Abstract The receptor pharmacology of the cardiovascular effects of dopexamine hydrochloride in the anaesthetized dog (given by i.v. infusion of 3 times 10−9-10−7 mol kg−1 min−1) has been analysed by the use of selective receptor antagonists and of ganglionic blockade. The increases in cardiac output, contractility, and rate were antagonized by the β2-adrenoceptor antagonist, ICI 118551. Renal blood flow rose secondary to reduction in renal vascular resistance and this was antagonized by SCH 23390, a highly selective DA1-receptor antagonist. Peripheral vasodilation and reduction of blood pressure were mediated by a combination of DA1 and DA2-receptor and β2-adrenoceptor stimulation. In a separate group of dogs, the cardiac stimulant effects of dopexamine HCl were partially reflex and were reduced by ganglion block, revealing responses due to stimulation of cardiac β2-adrenoceptors. Thus the β2-adrenoceptor agonist action of dopexamine HCl is not only partly responsible for afterload reduction but also leads to direct cardiac stimulation. From its cardiovascular profile, dopexamine HCl is likely to be of use in acute treatment of heart failure.