Mechanism of the pressor action of LY171555, a specific dopamine D2 receptor agonist, in the conscious rat

S Nagahama, YF Chen, MD Lindheimer and S Oparil

Administration of LY171555, a specific dopamine D2 receptor agonist, (10-1000 micrograms/kg i.v.) produced dose-related increases in mean arterial pressure in conscious Sprague-Dawley rats. Pretreatment with metoclopramide (5 mg/kg i.v.) abolished the pressor action of LY171555, whereas pretreatment with domperidone (2.5 mg/kg i.v.) and propranolol (10 mg/kg i.p.) did not affect the pressor action of LY171555. The vasopressor antagonist of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP (10 micrograms/kg i.v.) and phenoxybenzamine (1 mg/kg i.v.) partly blocked and hexamethonium (25 mg/kg i.v.) enhanced the pressor action of LY171555. After combined treatment with both d(CH2)5Tyr(Me)AVP and phenoxybenzamine, LY171555 induced a depressor response which was completely blocked by pretreatment with domperidone. LY171555 administration induced a rapid, short-acting depressor response followed by a pressor response in conscious adrenomedullectomized Sprague-Dawley rats which was smaller in magnitude than that seen in intact Sprague-Dawley rats. LY171555 administration increased plasma norepinephrine, epinephrine and AVP in conscious Sprague-Dawley rats. These results suggest that the pressor action of LY171555 in conscious rats is dependent on activation of sympathetic outflow and AVP release through the central D2 dopaminergic system and that the central pressor effects of LY171555 could mask a depressor effect of LY171555 at the peripheral D2 dopamine receptor.

Volume 236, Issue 3, pp. 735-742, 03/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics