Physiological role of nitric oxide in regulation of renal function
in humans.
Haynes, William G., Malcolm F. Hand, Mark E. C. Dockrell, David W.
Eadington, Michael R. Lee, Ziad Hussein, Nigel Benjamin and David J.
Webb.
Clinical Pharmacology Unit and Research Centre, Western General
Hospital, University of Edinburgh, Edinburgh EH4 2XU; *Department of
Clinical Pharmacology, Glaxo-Wellcome, Beckenham BR3 3BS; and
[grave]aDepartment of Clinical Pharmacology, St BartholomewOs
Hospital, London EC1A 7BE, United Kingdom
APStracts 3:0221F, 1996.
The physiological role of endogenous nitric oxide in regulation of
renal function in humans is unclear. Eight healthy men received an
inhibitor of nitric oxide synthase (L-NMMA; 3 mg/kg) and saline
placebo intravenously on two occasions. L-NMMA significantly
increased mean arterial pressure (+7%) and total peripheral
resistance (+36%). However, because renal plasma flow did not
decrease significantly, the increase in renal vascular resistance
(+21%) was significantly less than the increase in total peripheral
resistance. Glomerular filtration rate (-19%), filtration fraction (
-10%), urine flow rate (-18%), sodium (-28%) and free water excretion
(-25%) all decreased significantly. Fractional distal, but not
proximal, sodium reabsorption increased. L-NMMA also significantly
decreased plasma nitrate and urinary nitrate and dopamine excretion.
There were no significant changes in plasma renin activity, plasma
endothelin and aldosterone, or in platelet number and ex vivo
aggregation. L-NMMA had a plasma half-life of 75 min. Basal
generation of nitric oxide appears to contribute less to vascular
tone in the kidney than systemically, but may alter afferent
arteriolar tone. Decreased fractional sodium excretion supports an
important physiological role for nitric oxide in inhibition of
tubular sodium reabsorption, possibly mediated by the renal
dopaminergic system.
Received 19 August 1996; accepted in final form 19 November 1996
APS Manuscript Number F241-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996