Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans

Abstract

The renal functional changes following infusion of dopamine are well documented. The most pronounced effect is the increase in renal blood flow and a marked natriuretic response. Due to its specific renal effects, dopamine has become one of the most frequently used drugs in the treatment of critically ill patients with low cardiac output states and/or acute oliguric renal failure. Pharmacological effects of dopamine are dose dependent. Low doses of dopamine predominantly stimulate dopaminergic receptors, but with increasing doses actions secondary to stimulation of adrenergic beta(1) and alpha receptors also appear. Dopamine receptors are classified into the D1 and the D2 subtype families. Stimulation of D1 receptors increases adenylate cyclase activity and intracellular levels of cAMP, whereas D2 receptor activation decrease or do not change adenylate cyclase activity. In the kidney, dopamine receptors have been localized in the renal vasculature except in glomeruli and in the tubules (the proximal tubule > macula densa > the loop of Henle > the distal tubule > collecting ducts). The postsynaptic D1 receptor mediates vasodilation by a direct mechanism, whereas the presynaptic D2 receptor indirectly may dilate the vessels by inhibition of norepinephrine release. Consistent with previous results in animals, the present haemodynamic studies revealed that dopamine in normal subjects elicits a dose dependent biphasic effect on the mean arterial blood pressure. With 1 and 2 micrograms/kg/min, a depressor effect resulted from a decrease in the diastolic pressure, whereas a pressor effect, seen with doses at and above 7.5 micrograms/kg/min, was mainly caused by elevations of the systolic pressure. The studies indicated that the increase in cardiac output at low doses of dopamine is secondary to a decrease in peripheral vascular resistance, independent of effects of beta(1) receptors on cardiac contractility and heart rate. Dose-response studies demonstrated that the dopamine-induced increase in effective renal plasma flow (ERPF) reaches its maximum at 3 micrograms/kg/min. The increase in ERPF remained unchanged by pretreatment with metoprolol, and a comparison of dopamine and dobutamine in doses producing similar increases in cardiac output demonstrated that only dopamine increased ERPF. These findings indicate that indirect haemodynamic effects secondary to increases in cardiac contractility and cardiac output do not contribute significantly to the increase in renal perfusion caused by dopamine. In normal subjects, acute hypoxaemia attenuated the renal vasodilating effect of dopamine. The well known natriuretic effect of dopamine was significantly expressed in all of our studies, in which doses ranging from 1 to 5 micrograms/kg/min caused about a two-fold increase in sodium excretion. At doses at and above 7.5 micrograms/kg/min which increased mean arterial pressure, dopamine further increased sodium clearance (CNa) while ERPF was decreasing, indicating the contribution of pressure natriuresis at these high doses. Although not affecting the percentage increase in CNa, metoprolol suppressed the absolute, maximal response to non-pressor doses of dopamine, suggesting that a reduced adrenergic beta(1) receptor activity may indirectly affect the natriuretic response, probably by decreasing renal perfusion pressure. Previous studies in animals demonstrated that dopamine natriuresis can occur independent of increases in ERPF and GFR, and, furthermore, that the response can be abolished by specific D1 receptor antagonists. Evidence obtained by in vitro studies indicated that dopamine via D1 receptors may inhibit the Na(+)-H+ antiport at the brush-border membrane of proximal tubular cells and the Na(+)-K(+)-ATPase activity at basolateral membranes of both the proximal tubule and the medullary thick ascending limb of the loop of Henle. (ABSTRACT TRUNCATED)