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

Niels Vidiendal Olsen, Michael Hecht Olsen, Jan Bonde, Inge Lis Kanstrup, Inger Plum, Svend Strandgaard, Paul P. Leyssac

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    Abstrakt

    Aims: 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 m the range 0 to 12.5 μg 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 μg 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 μg kg-1 min-1 dose onwards. Effective renal plasma flow increased with all doses of dopamine, but peaked with the 3 μg kg-1 min-1 infusion rate [from 617 (585-649) ml mm-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 μg 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 μg 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 μg kg-1 min-1. The dose-dependent attenuation seen with higher doses is consistent with an increased α-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.

    OriginalsprogEngelsk
    Sider (fra-til)509-520
    Antal sider12
    TidsskriftBritish Journal of Clinical Pharmacology
    Vol/bind43
    Udgave nummer5
    StatusUdgivet - 9 jun. 1997

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