Blood pressure lowering effects of N,N-di-n-propyl-dopamine in rats: evidence for stimulation of peripheral dopamine receptors leading to inhibition of sympathetic vascular tone.
In conscious or pentobarbital-anesthetized hypertensive or normotensive rats, N,N-di-n-propyl-dopamine (DPDA) produced sustained decreases in mean systemic arterial blood pressure. In anesthetized normotensive animals, these responses were not significantly changed by vagotomy, desipramine, indomethacin, methylatropine, promethazine or propranolol, were markedly reduced by phenoxybenzamine or phentolamine, were entirely blocked by domperidone, haloperidol or sulpiride and were reverted to an alpha adrenoceptor-mediated pressor response after removal of central sympathetic tone. In phenoxybenzamine-pretreated pithed rats in which the blood pressure was elevated to prepithing levels with vasopressin, DPDA, in contrast to dopamine, produced no hypotensive effect. In the pithed rat, DPDA reduced the pressor responses elicited by electrical stimulation of the spinal cord and this effect was inhibited by haloperidol or sulpiride. DPDA slightly enhanced the pressor effects of norepinephrine but modified neither the blood pressure increases produced by epinephrine, phenylephrine, 5-hydroxytryptamine or angiotension II nor the vasodepressor effects of acetylcholine, histamine or salbutamol. Intracerebroventricular administration of DPDA produced blood pressure decreases which were slightly smaller in magnitude but longer in duration than those elicited by i.v. DPDA. However, DPDA leaked from the cerebroventricular space into the peripheral circulation. These results indicate that in the rat DPDA lowers blood pressure via activation of peripheral dopamine receptors possibly located presynaptically on vascular sympathetic neurons. The stimulation of these receptors induces a decrease in norepinephrine release which in turn is followed by a passive relaxation of the vascular beds under active sympathetic constriction.
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000294:innervation*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000959:Antihypertensive Agents; D011954:Receptors, Dopamine; C020895:N,N-di-n-propyldopamine; D010424:Pentobarbital; D004298:Dopamine