Effect of dietary protein on the renal response to fenoldopam in diabetic rats.
The effect of the dopamine D1 receptor agonist, fenoldopam, was studied in streptozotocin-induced diabetic rats treated with insulin to maintain a moderate hyperglycemia and fed a low, normal or high protein diet. Fenoldopam at 1 microgram/kg per min i.v. resulted in a significant increase in both glomerular filtration rate (GFR) and renal blood flow (RBF) in diabetic rats fed a normal protein diet. In rats fed a low protein diet, fenoldopam failed to alter either parameter, however, there was a very significant increase in both GFR and RBF in diabetic rats fed a high protein diet. Since diabetes is associated with a decrease in both urinary dopamine excretion as well as the hyperemic response to protein ingestion, it is possible that stimulation of dopamine D1 receptors by fenoldopam restores renal functional reserve in diabetic animals. The observation that the dopamine D1 receptor antagonist, SCH 23390, at a dose (1 microgram/kg per min) that abolished the renal vasodilator effects of fenoldopam, failed to alter renal hemodynamics in diabetic rats suggests that endogenous dopamine has little effect.
Wang
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YX
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Brooks
D P
DP
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004044:Dietary Proteins / Q000494:pharmacology*; D018818:Fenoldopam; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001552:Benzazepines; D004044:Dietary Proteins; D017447:Receptors, Dopamine D1; D014665:Vasodilator Agents; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam