Effects of a nitric oxide synthesis inhibitor on renal sodium handling and diluting capacity in humans.
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+/-10 to 34+/-5 micromol/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 reductions 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 medullary vasoconstriction, similar to that described for angiotensin II.
Dijkhorst-Oei
L T
LT
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Koomans
H A
HA
D000328:Adult; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D004032:Diet; D004231:Diuresis / Q000187:drug effects*; D004791:Enzyme Inhibitors; D006439:Hemodynamics; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009318:Natriuresis / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009994:Osmolar Concentration; D012016:Reference Values; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D019001:Nitric Oxide Synthase; D012083:Renin