CARDIOVASCULAR CHARACTERIZATION OF THE DA2DOPAMINE RECEPTOR AGONIST QUINPIROLE IN RATS
Authors: LEFEVRE‐BORG F. , LORRAIN J. , LECHAIRE J. , THIRY C. , LHOSTE F. , HICKS P. E. , CAVERO I. 
Published: August 2009

Summary—In normotensive anesthetized rats, 15‐min IV infusions of quinpirole (2.5–40.0 μg/kg/min) produced dose‐related, rapidly appearing, and long‐lasting decreases in mean carotid artery BP and HR. Hemodynamically, the hypotensive effects of quinpirole (10.0 μg/kg/min) were due to a fall in total peripheral vascular resistance inasmuch as CO did not undergo significant changes. Mesenteric, hindquarter, and renal blood flows were, respectively, reduced, unchanged, and increased by quinpirole; thus, the renal vascular resistance fell more than either the total peripheral or hindquarter vascular resistance. Biochemically, the hypotensive effects of quinpirole were accompanied by a decrease in the plasma level of norepinephrine and plasma renin activity. The peak fall in blood pressure produced by quinpirole was not significantly modified by atenolol, idazoxan, ranitidine, SCH 23390 (DA1dopamine receptor antagonist), enalapril, or SK&F 100273 (V1vasopressin receptor antagonist), but was entirely blocked byS‐sulpiride or removal of autonomic nerve drive to the cardiovascular system with chlorisondamine. The effect of quinpirole on systemic and regional vascular resistances was antagonized byS‐sulpiride. Furthermore, SK&F 100273 prevented the fall in mesenteric flow produced by quinpirole. Intracerebroventricular injection of quinpirole (10.0 μg/kg over 2 min) in saline‐ or SK&F 100273‐pretreated rats produced the same hypotensive effects as an identical IV dose of the compound. In pithed rats, quinpirole (10 μg/kg/min IV over 15 min) decreased pressor responses to electrical stimulation of spinal cord outflow without affecting those to exogenously injected angiotensin II, B‐HT 920, cirazoline, norepinephrine, or 5‐hydroxytryptamine. This inhibitory effect was antagonized byS‐sulpiride. The bradycardia produced by quinpirole in intact rats was mediated by the autonomic nervous system inasmuch as it was slightly modified by bilateral vagotomy, partly reduced by atenolol, and entirely prevented by pithing even when the low HR of the last preparation had been raised by IV infusion of isoprenaline. Furthermore,S‐sulpiride, but not SCH 23390 or idazoxan, antagonized this effect. In pithed rats, quinpirole similarly inhibited the tachycardic responses elicited by electrical stimulation of either the spinal cord outflow (preganglionic) or postganglionic cardioaccelerator nerve fibers. This effect of quinpirole was susceptible toS‐sulpiride but not idazoxan blockade. Finally, in conscious spontaneously hypertensive rats (SHR) but not in normotensive rats, quinpirole (10 μg/kg/min IA over 15 min) lowered blood pressure. This effect was significantly enhanced by SK&F 100273 and blocked by haloperidol. In conclusion, the BP and HR effects of quinpirole are mediated by stimulation of DA2dopamine receptors which, by blunting sympathetic nerve activity, leads to hypotension and bradycardia. Moreover, quinpirole‐evoked vasopressin release produces a functional antagonism of the effects of quinpirole on mesenteric blood flow in pentobarbital‐anesthetized rats and on BP in conscious SHR.