CHARACTERIZATION OF THE HYPOTENSIVE ACTION OF DOPAMINE RECEPTOR AGONISTS FENOLDOPAM AND QUINPIROLE IN ANAESTHETIZED RATS

Abstract

The present study was designed to examine the cardiovascular actions of fenoldopam, a DA1-receptor agonist, and quinpirole, a DA2 receptor agonist, in pentobarbital-anesthetized rats. Fenoldopam (20, 40 and 80 .mu.g/kg) produced short lasting decreases in blood pressure accompanied by tachycardia. Quinpirole (20 and 80 .mu.g/kg) caused hypotension and bradycardia which lasted throughout the one hour observation period. The DA1-receptor antagonist SCH 23390 almost completely abolished the hypotensive action of fenoldopam without affecting the hypotension or bradycardia seen with quinpirole. The mixed dopamine receptor antagonist, RS-sulpiride and the selective DA2-receptor antagonist, S-sulpiride, antagonized the cardiovascular actions of quinpirole. These compounds also blocked the hypotension seen with the lowest dose of fenoldopam, but this antagonism was of lesser magnitude than that produced by SCH 23390. Fenoldopam also produced hypotension when given to pithed rats after their resting blood pressure was restored to control level by noradrenaline infusion. This hypotension action of fenoldopam was antagonized by SCH 23390. Quinpirole, on the other hand, failed to exert any effect in pithed rats. Our results show that fenoldopam and quinpirole produce their cardiovascular actions via activation of DA1- and DA2-receptors, respectively. These selective dopamine receptor agonists and the selective DA1-receptor antagonist, SCH 23390 offer novel pharmacological probes for characterization of dopamine receptor subtypes in the kidney and other peripheral organs.