DOPAMINE NATRIURESIS IN SALT-REPLETED, WATER-LOADED HUMANS - A DOSE-RESPONSE STUDY

Aims The purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, re nal haemodynamics; and renal excretory function at infusion rates in t he range 0 to 12.5 mu g kg(-1) min(-1) in normal volunteers. Methods W hile undergoing water diuresis, eight subjects were infused with 0, 1, 2, 3, 5, 7.5, 10 or 12.5 mu g of dopamine kg(-1) min(-1) over 2 h in a randomized and double-blind fashion. On each study day, renal cleara nce studies were performed during a 1 h baseline period and subsequent ly during the second 1 h infusion period. Lithium clearance (CLLi) was used to estimate proximal tubular outflow. Results Cardiac output inc reased with the four highest doses. Mean arterial pressure followed a biphasic pattern with a decrease during the two lowest doses and a dos e-dependent increase from the 7.5 mu g kg(-1) min(-1) dose onwards. Ef fective renal plasma flow increased with all doses of dopamine, but pe aked with the 3 mu g kg(-1) min(-1) infusion rate [from 617 (585-649) ml min(-1) with placebo to 915 (824-1006) mi min(-1) (means with 95% C I, P < 0.001)]. None of the doses changed glomerular filtration rate ( GFR). Sodium clearance (CLNa) and CLLi were elevated with the four low est doses but increased further from 7.5 pg kg(-1) min(-1) onwards. Co mpared with placebo, the percentage increase in CLNa, with increasing dose was 77 (5-159), 93 (13-172), 107 (24-190), 121(60-181), 253 (65-4 41), 284 (74-494), and 212 (111-312) %, respectively. There were only small, inconsistent decreases in absolute proximal reabsorption rate ( APR = GFR-CLLi). Fractional distal reabsorption of sodium (FDRNa = (CL Li-CLNa)/CLLi) decreased with all doses, reaching its nadir with 7.5 m u g 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 mu g kg(-1) min(-1). The dose-dependent attenuatio n seen with higher doses is consistent with an increased alpha-adrener gic stimulation opposing the effect on dopaminergic receptors. The pre sent CLLi studies confirm that dopamine increases proximal tubular out flow. The results suggest that the natriuretic effect of depressor dos es of dopamine was primarily caused by attenuation of the increase in distal sodium reabsorption normally seen after an increase in proximal tubular outflow. Presser doses further increased sodium excretion, in dicating the presence of pressure natriuresis at these high doses.