Dopamine D-3 receptor activation modulates renal function in anesthetized rats

The renal effects of the D-3 receptor agonist R(+)-7-hydroxy-dipropyl-amino tetraline (7-OH-DPAT) were studied in anesthetized Sprague-Dawley rats usin g standard clearance experiments. 7-OH-DPAT infusion (0.01, 0.1, and 1.0 mu g kg(-1) min(-1)) dose-dependently increased glomerular filtration rate (G FR) compared to baseline by a maximum of 20+/-2% while arterial blood press ure was not affected. Heart rate was not altered during the two lower doses of 7-OH-DPAT whereas a slight reduction occurred due to infusion of 1.0 mu g kg(-1) min(-1). In contrast, higher doses of 7-OH-DPAT, starting from 3 mu g kg(-1) min(-1), markedly influenced systemic hemodynamics. In addition to the hyperfiltration, 7-OH-DPAT (1.0 mu g kg(-1) min(-1)) also induced a significant diuresis (27.7 +/- 4.3 mu l min(-1) 100 g(-1) vs 16.2 +/- 5.4 mu l min(-1) 100 g(-1)) and increased both absolute (3.30 +/- 0.58 mu mol m in(-1) 100 g(-1) vs 0.95 +/- 0.26 mu mol min(-1) 100 g(-1)) and fractional sodium excretion (2.48 +/- 0.32% vs 0.79 +/- 0.19%). These changes in renal function were not modulated by pretreatment with the D-2 receptor antagoni st S(-)-sulpiride but abolished by the D-3 antagonist 5,6-dimethoxy-2-(di-n -propylamino)indane (U-99194A). In coincidence with the action of 7-OH-DPAT on both glomerular and tubular function, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of D-3 receptors in both gl omerular and tubular fractions of kidneys taken from Sprague-Dawley rats. T hese data indicate that D-3 receptors in the kidney are involved in the reg ulation of renal hemodynamics and tubular function.