Comparison of the effects of the novel inotropic agent, ibopamine, with epinine, dopamine and fenoldopam on renal vascular dopamine receptors in the anesthetized dog.
The effect of i.v. administration of the novel, p.o. active inotropic prodrug, ibopamine, on canine renal vascular dopamine DA-1 receptors was determined in the anesthetized dog. These effects were compared with those produced by the active form of ibopamine, epinine, and with the standard DA-1 receptor agonists, dopamine and fenoldopam. After pretreatment of pentobarbital-anesthetized dogs with phenoxybenzamine (10 mg/kg i.v.) and propranolol (2 mg/kg i.v.) to block alpha and beta adrenoceptor-mediated effects, respectively, the renal blood flow responses to i.v. administration of ibopamine, epinine, dopamine and fenoldopam were determined before and after selective blockade of DA-1 receptors by i.v. infusion of SK&F R-83566 (0.5 microgram/kg/min). Under control conditions, ibopamine produced a dose-dependent increase in renal blood flow as a result of renal vasodilation (i.e., decrease in renal vascular resistance), and was approximately 10-fold less potent than epinine in this respect. Epinine elicited qualitatively similar renal hemodynamic changes to ibopamine with the exception of potency. Dopamine was approximately equipotent with epinine as a renal vasodilator, and both compounds were 10-fold less potent than fenoldopam. Concurrent with the renal vasodilation produced by all four compounds, there was a reduction in mean arterial blood pressure and total peripheral vascular resistance. After the administration of SK&F R-83566, the renal vasodilator responses to fenoldopam were antagonized markedly with an approximate 30-fold rightward shift in the log dose-response curve, whereas the renal vasodilator responses to dopamine were abolished completely and converted into small vasoconstrictor responses.(ABSTRACT TRUNCATED AT 250 WORDS)
D000758:Anesthesia; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001808:Blood Vessels / Q000378:metabolism; D002316:Cardiotonic Agents; D003846:Deoxyepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D018818:Fenoldopam; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D001552:Benzazepines; D002316:Cardiotonic Agents; D011954:Receptors, Dopamine; C023487:ibopamine; D018818:Fenoldopam; D003846:Deoxyepinephrine; D004298:Dopamine