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Am J Physiol Regul Integr Comp Physiol 275: R986-R994, 1998;
0363-6119/98 $5.00
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Vol. 275, Issue 4, R986-R994, October 1998

Effects of costimulation of dopamine D1- and D2-like receptors on renal function

Pedro A. Jose1, Laureano D. Asico1, Gilbert M. Eisner2,3, Felice Pocchiari4, Claudio Semeraro4, and Robin A. Felder5

1 Department of Pediatrics and 2 Department of Medicine, Georgetown University Medical Center; 3 Department of Medicine, Washington Hospital Center, Washington, District of Columbia 20007; 4 Department of Biochemistry, Zambon Group, Bresso, Italy 20091; and 5 Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

In vitro studies have suggested that dopamine D1- and D2-like receptors interact to inhibit renal sodium transport. We used Z-1046, a dopamine receptor agonist with the rank-order potency D3 >=  D4 > D2 > D5 > D1, to test the hypothesis that D1- and D2-like receptors interact to inhibit renal sodium transport in vivo in anesthetized rats. Increasing doses of Z-1046, administered via the right renal artery, increased renal blood flow (RBF), urine flow, and absolute and fractional sodium excretion without affecting glomerular filtration rate. For determination of the dopamine receptor involved in the renal functional effects of Z-1046, another group of rats received Z-1046 at 2 µg · kg-1 · min-1 (n = 10) in the presence or absence of the D2-like receptor antagonist domperidone and/or the D1-like antagonist SCH-23390. Domperidone alone had no effect but blocked the Z-1046-mediated increase in urine flow and sodium excretion; it enhanced the increase in RBF after Z-1046. SCH-23390 by itself decreased urine flow and sodium excretion without affecting RBF and blocked the diuretic, natriuretic, and renal vasodilatory effect of Z-1046. We conclude that the renal vasodilatory effect of Z-1046 is D1-like receptor dependent, whereas the diuretic and natriuretic effects are both D1- and D2-like receptor dependent.

dopamine receptors; sodium excretion; renal hemodynamics


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