Effects of systemic no-synthesis inhibition on renal plasma flow,
glomerular filtration rate, urinary excretion of sodium and
vasoactive hormones in healthy man.
Bech, J. N., C. B. Nielsen, and E. B. Pedersen.
RESEARCH LABORATORY FOR HYPERTENSION AND NEPHROLOGY, SKEJBY
HOSPITAL, UNIVERSITY HOSPITAL IN AARHUS, DK-8200 AARHUS N,
DENMARK
APStracts 2:0220F, 1995.
Animal studies have implicated an important role of nitric oxide (NO)
in the regulation of blood pressure, renal hemodynamics and renal
excretion of sodium. NG-monomethyl-L-arginine (L-NMMA) is a specific,
competitive inhibitor of NO-synthesis interfering with nitric oxide
synthase. The purpose of the present study was to investigate the
effect of L-NMMA on renal plasma flow (RPF), glomerular filtration
rate (GFR), urinary sodium excretion (UNa), fractional sodium
excretion (FE Na), fractional lithium excretion (FE Li), blood
pressure (MAP) and heart rate (HR) in healthy humans. In a randomized
placebo controlled study 23 healthy subjects were randomized to
receive either bolus injection of L-NMMA (3 mg/kg in 10 ml saline,
n=12) or placebo (10 ml saline, n=11). GFR and RPF were measured
using the renal clearances of 51Cr-EDTA and 125I-Hippuran by the
constant infusion technique. L-NMMA treatment induced 60 min. after
injection a 14.6 % decrease in RPF, a 5.8 % decrease in GFR, a 9.8 %
increase in filtration fraction, a 34.7 % decrease in UNa, a 28.6 %
decrease in FE Na and a 12.1 % decrease in FE Li. These changes were
still evident 120 min. after injection. None of the effect parameters
were changed after placebo except FENa which increased 9.9 % 60 min.
after injection Ten minutes after L-NMMA injection MAP increased
significantly (80 mmHg vs. 88 mmHg) and HR decreased (58 beats/min
vs. 47 beats/min). The changes in HR and MAP normalized within 30
min. L-NMMA significantly declined the plasma level of cGMP 60 min.
(3.0 vs. 3.7 pmol/L) and 120 min. after injection (2.5 pmol/L vs. 3.7
pmol/L). It is concluded that in healthy humans NO is a regulator of
renal hemodyna mics as a tonic vasodilator and a regulator of sodium
excretion at least partly due to a proximal tubular effect.
Received 14 September 1995; accepted in final form 5 December
1995.
APS Manuscript Number F314-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95