Effects of Dopamine on Renal Function in the Rat Isolated Perfused Kidney

Abstract

The renal effects of dopamine, the dopamine antagonist spiperone and the combination of dopamine and spiperone were examined in the isolated perfused rat kidney preparation. Studies were carried out at constant perfusion pressure and the following were measured at 10 min intervals for 1 h: perfusate flow; GFR (3H-inulin); urine flow rate; sodium, potassium and kallikrein excretion; perfusate renin concentration; perfusate and urinary-dopamine levels. Low-dose dopamine infusion (6 X 10(-10) mol/min) resulted in significant diuresis, natriuresis and kaluresis but little change in GFR. These effects were blocked by spiperone (10(-10) mol/min) which had no significant effects when infused alone. At a higher dose (10(-8) mol/min) dopamine significantly increased urine flow alone; this too was reversed by spiperone. Dopamine had no significant effects on perfusate flow, renin release or kallikrein excretion. Perfused control kidneys excreted amounts of dopamine (328 pmol/h, s.e.m. = 57, n = 6) far in excess of kidney dopamine content (49 pmol/g, s.e.m. = 6, n = 32). Renal handling of infused dopamine was dose-related; the fraction of the administered dose taken up and/or metabolized by the kidney on the higher dose infusion was considerably less than on the lower dose (40%, s.e.m. = 3 vs. 82%, s.e.m. = 6) while more was excreted (13%, s.e.m. = 3 vs. 2%, s.e.m. = 1). These studies indicate that dopamine at low doses can produce diuresis, natriuresis and kaluresis independently of extrarenal or haemodynamic influences and not mediated by renal renin or kallikrein systems. The kidney also exhibits a saturable capacity for dopamine uptake and/or metabolism.

Dopamine and Renal Function and Blood Pressure Regulation

“…The inhibitory effect of dopamine on ion transport is exerted via its own receptors (10, 83, 123, 173, 204, 210, 220, 352, 396, 401, 402, 457–459, 597, 628, 690) and via the regulation of the release or secretion of other hormones/humoral substances. Such hormones may directly inhibit ion transport, interact with dopamine to increase [e.g., ANP (118,318,392, 393,481), nitric oxide (631), prolactin (280), and eicosanoids (272, 328)] their inhibition of ion and water transport, and/or prevent their stimulatory effect on sodium transport [e.g., angiotensin II (100,101,116,134,274,321,363,558,628), insulin (44,45,682), and vasopressin (16,559)].…”

Manipulation of the Renal Circulation in Septic Shock

“…McGrath et al [51] could not produce increases in renal blood flow or glomerular filtration rate by the infusion of dopa mine in isolated perfused rat kidneys while main taining a constant perfusion pressure, but were able to induce increased sodium excretion. Davis et al [52] studied the mechanism of natriuresis in conscious dogs using microtubular pipettes.…”

Characterization of a dopamine receptor (DA2K) in the kidney inner medulla.

“…The natriuretic effects of DA are generally thought to be due to an increase in renal blood flow and glomerular filtration rate (1) but may include direct tubular effects since low doses of DA increase urine output and urinary sodium excretion without altering renal hemodynamics (3)(4)(5). Although the mechanism of action ofDA within the kidney is not resolved, the effects ofDA on the kidney are blocked by DA receptor antagonists (2,6,7).…”

“…Spiperone, a central nervous system D2 antagonist, blocks the DA-stimulated increase in renal blood flow and sodium excretion in isolated perfused rat kidney (4). Bromocriptine, a DA2 agonist, has been reported to increase renal blood flow and singlenephron glomerular filtration rate in the rat (12,13 (22) and are described in detail elsewhere (T.H.…”