EFFECT OF DIETARY-PROTEIN ON THE RENAL RESPONSE TO FENOLDOPAM IN DIABETIC RATS

The effect of the dopamine D-1 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 mu g/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 D-1 receptors by fenoldopam restores renal functional reserve in diabetic animals. The observation that the dopamine D-1 receptor antagonist, SCH 23390, at a dose (1 mu g/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.