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.