Primate cardiovascular responses mediated by dopamine receptors: effects of N,N-di-n-propyldopamine and LY171555.
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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; C020895:N,N-di-n-propyldopamine; D013469:Sulpiride; D004298:Dopamine