The cardiovascular actions of dopamine and the effects of central and peripheral catecholaminergic receptor blocking drugs

Abstract

The cardiovascular effects of dopamine (DA) were studied in anesthetized dogs with special attention to the susceptibility of these effects to inhibition by catecholaminergic receptor blocking drugs. Dopamine given by rapid i.v. injection at 1 and 3 mug/kg produced depressor responses whereas doses from 9 to 81 mug/kg produced pressor resposes and increases in cardiac contractile force. Propranolol inhibited the increases in cardiac contractility whereas phenoxybenzamine potentiated the depressor effect of low doses of DA and reversed the pressor effect of high doses. Bulbocapnine blocked the depressor effect of DA in both phenoxybenzamine and propranolol-treated dogs. Pimozide, however, had no effect on the depressor response to DA. In hemodynamic studies, DA reduced blood pressure, total peripheral resistance and renal vascular resistance. Cardiac output and renal blood flow were increased. Bulbocapnine, but not pimozide, abolished the effects of DA on blood pressure, vascular resistance and renal blood flow. In conscious dogs, pimozide abolished apomorphine-induced emesis (an effect mediated by DA receptors in the central nervous system) whereas bulbocapnine had no effect. Therefore, the peripheral vascular and central dopamine receptors may be pharmacologically distinct.