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.