Dopamine natriuresis in salt-repleted, water-loaded humans: a dose-response study.
OBJECTIVE
The 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 microg 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 microg 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 dose-dependent increase from the 7.5 microg kg(-1) min(-1) dose onwards. Effective renal plasma flow increased with all doses of dopamine, but peaked with the 3 microg kg(-1) min(-1) infusion rate [from 617 (585-649) ml min(-1) with placebo to 915 (824-1006) ml min(-1) (means with 95% CI, P<0.001)]. None of the doses changed glomerular filtration rate (GFR). Sodium clearance (CL(Na)) and CL(Li) were elevated with the four lowest doses but increased further from 7.5 microg kg(-1) min(-1) onwards. Compared with placebo, the percentage increase in CL(Na) with increasing dose was 77 (5-159), 93 (13-172), 107 (24-190), 121 (60-181), 253 (65-441), 284 (74-494), and 212 (111-312) %, respectively. There were only small, inconsistent decreases in absolute proximal reabsorption rate (APR = GFR-CL(Li)). Fractional distal reabsorption of sodium (FDR(Na) = (CL(Li)-CL(Na))/CL(Li)) decreased with all doses, reaching its nadir with 7.5 microg kg(-1) min(-1) [from 95.9 (94.6-97.2) % with placebo to 91.5 (90.0-93.0) % (P<0.01)] whereafter a flat dose-response curve was observed.


CONCLUSIONS
In conclusion, the renal vasodilating effect of dopamine was maximal with 3 microg kg(-1) min(-1). The dose-dependent attenuation seen with higher doses is consistent with an increased alpha-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.
Olsen
N V
NV
Department of Anaesthesia, Herlev Hospital, Denmark.
Olsen
M H
MH
Bonde
J
J
Kanstrup
I L
IL
Plum
I
I
Strandgaard
S
S
Leyssac
P P
PP
D000328:Adult; D000450:Aldosterone / Q000097:blood; D001834:Body Water / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D004298:Dopamine / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004573:Electrolytes / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008094:Lithium / Q000652:urine; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D002395:Catecholamines; D004573:Electrolytes; D000450:Aldosterone; D008094:Lithium; D012083:Renin; D004298:Dopamine