title: Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats.
abstract: Activation of renal dopamine-1 receptors decreases sodium transport. However, the spontaneously hypertensive rat retains sodium despite increased renal dopamine concentration. We tested the hypothesis that the abnormal sodium handling in spontaneously hypertensive rats (Okamoto-Aoki strain) is related to a decreased dopaminergic response by studying the effects of the intrarenal infusion of the dopamine-1 agonist SKF-38393 and the dopamine-1 antagonist SCH-23390 in hypertensive and in normotensive Wistar-Kyoto rats. Rats (9-16 weeks old) were studied with renal nerves intact under pentobarbital anesthesia (n = 5-6 in each group). Specificity of dopamine-1 effects of SKF-38393 was verified because its natriuretic effect was blocked in a dose-related manner by the dopamine-1 antagonist SCH-23390 (n = 5). Intrarenal but resulted in a dose-related natriuresis and diuresis in normotensive but not in hypertensive rats. Intrarenal arterial infusion of the dopamine-1 antagonist SCH-23390 alone induced an antinatriuresis, without affecting glomerular filtration rate, in normotensive but not in hypertensive rats. Addition of the dopamine-2 antagonist YM-09151 to the dopamine-1 antagonist infusion did not enhance the effect of the dopamine-1 antagonist. The lack of response to the dopamine-1 agonist or antagonist in hypertensive rats was not due to differences in renal dopamine-1 receptor density (1.3 +/- 0.3 pmol/mg protein for spontaneously hypertensive rats, n = 4; 1 +/- 0.2 for Wistar-Kyoto rats, n = 4) or affinity; distribution determined by autoradiography was also similar. The abnormal renal sodium handling in 9-16-week-old spontaneously hypertensive rats is in part due to decreased response distal to the dopamine-1 receptor.
authors.affiliation: Department of Pathology, University of Virginia Medical Center, Charlottesville.
authors.forename: R A
authors.initials: RA
authors.lastname: Felder
authors.forename: M G
authors.initials: MG
authors.lastname: Seikaly
authors.forename: P
authors.initials: P
authors.lastname: Cody
authors.forename: G M
authors.initials: GM
authors.lastname: Eisner
authors.forename: P A
authors.initials: PA
authors.lastname: Jose
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000032:analysis / Q000187:drug effects; D017447:Receptors, Dopamine D1; D012044:Regression Analysis; D014563:Urodynamics / Q000187:drug effects
chemical_list: D001549:Benzamides; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C030265:nemonapride