title: Comparison of the effects of the novel inotropic agent, ibopamine, with epinine, dopamine and fenoldopam on renal vascular dopamine receptors in the anesthetized dog.
abstract: 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)
mesh_terms: 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
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D011954:Receptors, Dopamine; C023487:ibopamine; D018818:Fenoldopam; D003846:Deoxyepinephrine; D004298:Dopamine