Dopamine D3 receptor activation modulates renal function in anesthetized rats

Abstract

The renal effects of the D₃ receptor agonist R(+)-7-hydroxy-dipropyl-aminotetraline (7-OH-DPAT) were studied in anesthetized Sprague-Dawley rats using standard clearance experiments. 7-OH-DPAT infusion (0.01, 0.1, and 1.0 µg kg^–1 min^–1) dose-dependently increased glomerular filtration rate (GFR) compared to baseline by a maximum of 20±2% while arterial blood pressure 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 µg kg^–1 min^–1. In contrast, higher doses of 7-OH-DPAT, starting from 3 µg kg^–1 min^–1, markedly influenced systemic hemodynamics. In addition to the hyperfiltration, 7-OH-DPAT (1.0 µg kg^–1 min^–1) also induced a significant diuresis (27.7±4.3 µl min^–1 100 g^–1 vs 16.2±5.4 µl min^–1 100 g^–1) and increased both absolute (3.30±0.58 µmol min^–1 100 g^–1 vs 0.95±0.26 µmol 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 D₂ receptor antagonist S(–)-sulpiride but abolished by the D₃ 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 D₃ receptors in both glomerular and tubular fractions of kidneys taken from Sprague-Dawley rats. These data indicate that D₃ receptors in the kidney are involved in the regulation of renal hemodynamics and tubular function.