Administration of
N,N-di-n-propyldopamine (
DPDA) (1-100 micrograms/kg i.v.) and LY171555 (1-100 micrograms/kg i.v.) produced dose-related arterial
hypotension accompanied by
bradycardia in anesthetized rhesus monkey. The cardiovascular effects of
DPDA were of brief duration, whereas
hypotension and
bradycardia induced by LY171555 were sustained. Pretreatment of monkeys with
sulpiride (0.5 mg/kg i.v.) abolished the blood pressure and cardiac rate-lowering effects of
DPDA and LY171555. During the time course of cardiovascular alterations produced by LY171555 (100 micrograms/kg i.v.), increments in cardiac rate due to electrical stimulation of the right stellate ganglion were inhibited. This effect also was abolished by
sulpiride treatment. The antagonism of neural
tachycardia by LY171555 was selective, as the
drug had no concomitant inhibitory action on cardiac rate or diastolic blood pressure responses to exogenous
norepinephrine. Hemodynamic analysis demonstrated that
DPDA (20-200 micrograms/kg i.v.) and LY171555 (1-10 micrograms/kg i.v.) each lowered arterial blood pressure, without reflex
tachycardia, by dilating the systemic vasculature; cardiac output and stroke volume were maintained. Furthermore, left ventricular minute work and
stroke work were reduced by each
drug in association with systemic
hypotension. The data suggest that
DPDA and LY171555 produce cardiovascular responses by inhibiting neurogenic release of
norepinephrine through an interaction with D-2
dopamine receptors. The present primate data also support the potential clinical utility of
dopamine receptor agonists in treating
cardiovascular disease.