Dopamine natriuresis in salt-repleted, water-loaded humans: a dose-response study

Abstract

AimsThe purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 mg kg −1 min −1 in normal volunteers. Methods While undergoing water diuresis, eight subjects were infused with 0, 1, 2, 3, 5, 7.5, 10 or 12.5 mg of dopamine kg −1 min −1 over 2 h in a randomized and double-blind fashion. On each study day, renal clearance studies were performed during a 1 h baseline period and subsequently during the second 1 h infusion period. Lithium clearance (CL Li ) was used to estimate proximal tubular outflow.Results Cardiac output increased with the four highest doses. Mean arterial pressure followed a biphasic pattern with a decrease during the two lowest doses and a dosedependent increase from the 7.5 mg kg Conclusions In conclusion, the renal vasodilating effect of dopamine was maximal with 3 mg kg −1 min −1 . The dose-dependent attenuation seen with higher doses is consistent with an increased a-adrenergic stimulation opposing the effect on dopaminergic receptors. The present CL Li studies confirm that dopamine increases proximal tubular outflow. The results suggest that the natriuretic effect of depressor doses of dopamine was primarily caused by attenuation of the increase in distal sodium reabsorption normally seen after an increase in proximal tubular outflow. Pressor doses further increased sodium excretion, indicating the presence of pressure natriuresis at these high doses.Keywords: renal haemodynamics, kidney function, natriuresis, dopamine, dose-response, tubular function, lithium clearance, sodium hydronephrotic kidney of the rat [4], thus supporting the Introduction concept of a vasodilating effect of specific dopaminergic D 1 -receptor activation, which at higher doses is opposed by In anaesthetized dogs [1] and rats [2], low doses of dopamine decreased renal vascular resistance, whereas higher doses an action of a-adrenergic receptors [5,6]. Another important effect of dopamine, which does not occur with other caused vasoconstriction. a-adrenergic receptor blockade abolished the vasoconstriction so that vasodilation was catecholamines, is the increase in sodium excretion [5][6][7]. Stimulation of D 1 -receptors in proximal tubular brushobserved with all doses of dopamine [2]. These dosedependent effects have been confirmed in studies using border membranes inhibits the Na

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

“…53 Fenoldopam's natriuretic effect on a HS diet is related, perhaps, to decreased proximal and distal sodium transport, as shown previously. 22,24,32 Enalapril did not cause natriuresis on either diet at the dose employed. Higher doses (20 mg) of enalapril cause natriuresis in humans on 10-300 mmol Na + /day but not on 400 mmol Na + /day.…”

“…[18][19][20][21][22][24][25][26]31,32,34,39 Selective gene deletion of aromatic amino acid decarboxylase (essential for renal dopamine synthesis) in the renal proximal tubule in mice produces salt-sensitive hypertension, 43 underscoring the importance of dopamine synthesis by the proximal tubule in sodium homeostasis and BP regulation. Renal dopamine increases with acute and chronic salt loading 44 and acts on D 1 -like 45 and D 2 -like 46 dopamine receptors, causing natriuresis.…”

“…Renal dopamine increases with acute and chronic salt loading 44 and acts on D 1 -like 45 and D 2 -like 46 dopamine receptors, causing natriuresis. [18][19][20][21][22][24][25][26]31,32,34,39 The natriuretic effect of dopamine is impaired in salt-depleted states. 46,47 We submit evidence, for the first time in normotensive (,120/80 mmHg) 48 salt-resistant humans, 33 that the RAS and dopaminergic system interact in regulating renal sodium transport on LS and HS diets.…”

“…[22][23][24] During salt restriction, the ability of renal endogenous dopamine to inhibit sodium transport is abolished. 22 This phenomenon is attributable to decreased renal dopamine production, altered dopamine receptor subtype expression, and postreceptor mechanisms in the renal tubule, and to overriding effects of salt-conserving mechanisms such as the sympathetic nervous system, the RAAS, and other saltretaining hormones.…”

“…[24][25][26][27][28] Dopamine can also negatively regulate renin production, 29 while angiotensin II (AT 2 ) can increase dopamine turnover. 30 By contrast, D 1 -like and AT 2 receptors cooperate to inhibit renal proximal sodium transport, 31 causing natriuresis.…”