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

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 D 1 - and D 2 -like receptors interact to inhibit renal sodium transport. We used Z-1046, a dopamine receptor agonist with the rank-order potency D 3 D 4 > D 2 > D 5 > D 1 , to test the hypothesis that D 1 - and D 2 -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 D 2 -like receptor antagonist domperidone and/or the D 1 -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 D 1 -like receptor dependent, whereas the diuretic and natriuretic effects are both D 1 - and D 2 -like receptor dependent. dopamine receptors; sodium excretion; renal hemodynamics