Activation of peripheral dopamine presynaptic receptors lowers blood pressure and heart rate in dogs.

Previous studies have identified several N,N-dialkyl substituted analogs of dopamine that lower blood pressure and cause renal and femoral vasodilation by activation of noradrenergic neuronal dopaminergic receptors that inhibit further release of norepinephrine (presynaptic DA 2 ) or of vasodilatory dopaminergic receptors located in vascular beds (postsynaptic DA|).Unlike dopamine itself, these analogs demonstrate minimal /3,-adrenergic receptor activation and a!-vasoconstrictor effect.In the present study, we have compared the relative hemodynamic, renal and emetic properties of four of these dopamine analogs in anesthetized and/or conscious dogs.The purposes of the studies were: 1) determination of the relative contribution of central versus peripheral nervous system sites of action of these analogs to their effects on cardiovascular function; 2) assessment of the relative importance of activation of DA, versus DA 2 receptors for the observed hemodynamic effects; and 3) investigation of the relative efficacy of dopamine antagonists for DA 2 versus DA, receptors.The reduction in blood pressure, increase in renal blood flow, and decrease in renal vascular resistance produced by propylbutyl -(PBDA), ethylbutyl-(EBDA), or propylpentyl-(PPDA) dopamine was similar to that reported previously for dipropyldopamine (DPDA).All analogs except PPDA also lowered heart rate.Doses of either the peripheral dopamine receptor antagonist, domperidone, or the peripheral and central dopamine receptor antagonist, metoclopramide, which attenuated PBDA-induced reductions in mean arterial pressure and heart rate did not antagonize the increase in renal blood flow produced by this analog.Following electrical stimulation of the cardioaccelerator nerve, all four dopamine analogs reduced the heart rate of spinally transected, vagotomized, anesthetized dogs.In addition, ( -)-sulpiride but not phentolamine antagonized the reduction in both heart rate and coronary sinus norepinephrine secretion produced by PBDA during cardioaccelerator nerve stimulation.In conscious dogs, the emetic potency was: DPDA > PPDA = PBDA > EBDA.The dopamine receptor antagonist, (-)-sulpiride, completely abolished the emesis induced by PBDA administration.These results indicate that PBDA and other N,N-dialkyl substituted dopamine derivatives can alter cardiovascular hemodynamics primarily by agonism of peripheral dopamine receptors.Furthermore, PBDA appears to lower blood pressure primarily through agonism of presynaptic DA 2 receptors rather than postsynaptic DA, vascular receptors.(Hypertension 5: 226-234, 1983) KEY WORDS • propylbutyldopamine *