Antagonism of the renal vasodilator activity of dopamine by metoclopramide

Abstract

The interaction of metoclopramide with renal dopamine receptors has been characterized in anesthetized dogs surgically prepared with arterial blood pressure catheters and renal artery blood flowprobes. In normal dogs, i.v. dopamine (3 microgram/kg) produced consistent and selective decrements in renal vascular resistance (RVR) and increments in renal blood flow over a 220 min test period; mean arterial blood pressure and cardiac rate were minimally affected. Pretreatment with metoclopramide, 1 and 10 mg/kg i.v., resulted in dose-related inhibition (maximum inhibition 44% and 94%, respectively) of the renal vasodilator activity of dopamine without altering baseline parameters. The duration of antagonism produced by 1 mg/kg of metoclopramide was approximately 30 min, while 10 mg/kg resulted in significant attenuation for the entire test period. Decreases in RVR produced by prostaglandin A1 (0.03 and 0.3 microgram/kg, i.v.) and bradykinin (3 and 15 microgram/kg, i.v.) that were comparable to those of dopamine were unaltered by metoclopramide. Furthermore, metoclopramide did not affect the diastolic blood pressure responses to noradrenaline (0.2-3 microgram/kg, i.v.) or isoproterenol (0.03-0.3 microgram/kg, i.v.), nor did it alter dopamine-induced vasoconstriction of the iliac vasculature. In phenoxybenzamine (3 mg/kg, i.v.) treated dogs, dopamine (0.3-30 microgram/kg, i.v.) produced dose-related reductions in RVR. Administration of metoclopramide (10 mg/kg, i.v.) resulted in a 10-fold parallel displacement, to the right, of the RVR dose-response curve to dopamine. These findings demonstrate that metoclopramide is an effective antagonist of renal dopamine receptors following systemic administration in the dog. The results are not consistent with the classification of metoclopramide as a selective antagonist of D-2 receptors.