Nephrology Dialysis Transplantation, Vol 13, Issue 3 587-593, Copyright © 1998 by Oxford University Press
L Dijkhorst-Oei and H Koomans
Background: Inhibition of nitric oxide (NO) synthesis
has antinatriuretic and antidiuretic effects. Limited information is
available on the role of NO in tubular sodium transport in the human
kidney. Methods: We studied nine healthy,
sodium-replete males with clearance techniques during maximal diuresis.
NG-monomethyl-L-arginine
(L-NMMA, 3 mg/kg priming dose plus 3 mg/kg/h) was
infused for 3 h, to achieve steady-state inhibition of NO synthesis. Data
were compared with a time control study. Results: The
effects of L-NMMA were quickly established and
persisted through the entire infusion period. Mean arterial pressure
increased slightly from 85±3 to 91±3 mmHg
(P<0.05). Renal plasma flow decreased substantially, and glomerular
filtration rate slightly. Large decreases in absolute sodium excretion,
from 79&;plusmn;10 to 34±5 &mgr;mol/min (P<0.01),
and fractional sodium excretion, from 0.5±0.0 to
0.3±0.0% (P<0.01), were associated with significant
reduction in fractional lithium excretion (P<0.05) and maximum urine
flow (P<0.01). Minimal urine sodium concentration decreased from
5.8±0.04 to 3.9±0.4 mmol/l (P<0.01) whereas
minimal urine osmolality increased (P<0.05). Plasma renin activity,
aldosterone and atrial natriuretic peptide levels did not change, whereas
urinary excretions of guanosine 3'5'-cyclic monophosphate and of nitrite
plus nitrate decreased slightly. Conclusions:
Inhibition of endogenous NO synthesis in humans to an extent that raises
blood pressure only mildly causes antinatriuresis, that can be attributed
to increases in sodium reabsorption both at proximal and distal nephron
sites. In addition, renal diluting capacity decreases. The effects in the
diluting segment have not been reported before, and may be due to medullar
vasoconstriction, similar to that described for angiotensin II.
Key words: blood pressure; lithium;
L-NMMA; maximal diuresis; renal haemodynamics
ORIGINAL ARTICLES
Effects of a nitric oxide synthesis inhibitor on renal sodium handling and diluting capacity in humans
Department of Nephrology and Hypertension, University Hospital Utrecht, Room F03.226, PO Box 85500, 3508 GA Utrecht, The Netherlands; Corresponding author
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