Characterization of the hypotensive action of dopamine receptor agonists fenoldopam and quinpirole in anaesthetized rats.
The present study was designed to examine the cardiovascular actions of fenoldopam, a DA1-receptor agonist, and quinpirole, a DA2 receptor agonist, in pentobarbital-anaesthetized rats. Fenoldopam (20, 40 and 80 micrograms/kg) produced short lasting decreases in blood pressure accompanied by tachycardia. Quinpirole (20 and 80 micrograms/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 hypotensive action of fenoldopam was antagonised 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.
Sengupta
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S
Lokhandwala
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MF
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004873:Ergolines / Q000494:pharmacology*; D018818:Fenoldopam; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology
D000959:Antihypertensive Agents; D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D013469:Sulpiride; D018818:Fenoldopam