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Nitric Oxide Synthesis Inhibition Does Not Impair Water Immersion-Induced Renal Vasodilation in Humans

Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.

Correspondence to Dr. Hein A. Koomans, Department of Nephrology and Hypertension, University Hospital Utrecht, Room F03.226, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Phone : +31 30 2507329 ; Fax : +31 30 2543492 ; E-mail : H.A.Koomans{at}DIGD.AZU.NL

Abstract. Nitric oxide (NO) is tonically released in the kidney to maintain renal perfusion and adequate sodium and water clearance. Little is known about the role of NO in the renal adaptation to an acute volume challenge. This is important for our understanding of pathophysiologic conditions associated with impaired NO activity. This study examined the effects of NO synthesis inhibition on neurohumoral, renal hemodynamic, and excretory responses to head-out immersion (HOI). Seven healthy men underwent four 7-h clearance studies. One study served as a time control study (placebo infusion), and in one study N^G-monomethyl-L-arginine (L-NMMA ; 3 mg/kg priming dose + 3 mg/kg per h) was infused during hours 2 to 5. In a third and fourth clearance study, HOI was applied from hours 3 to 5, during infusion of either placebo or L-NMMA. To assess the degree of NO synthesis inhibition, the effect of L-NMMA on [¹⁵N]-arginine-to-[¹⁵N]-citrulline conversion rate was studied in four others. HOI decreased mean arterial pressure (MAP) from 87 ± 3 to 76 ± 2 mmHg and renal vascular resistance (RVR) from 82 ± 6 to 70 ± 7 mmHg · min/L, and increased sodium excretion (UNaV) from 110 ± 27 to 195 ± 29 µmol/min and flow (UV) from 14.4 ± 1.4 to 15.8 ± 1.4 ml/min. L-NMMA caused profound and sustained increases in MAP and RVR and decreases in UNaV and UV. HOI superimposed on L-NMMA infusion decreased the elevated MAP from 93 ± 4 to 83 ± 2 mmHg and RVR from 111 ± 9 to 95 ± 7 mmHg · min/L, and increased UNaV from 41 ± 8 to 95 ± 15 µmol/min and UV from 10.0 ± 1.1 to 12.7 ± 1.4 ml/min. The relative changes were not significantly different from the effects of HOI without L-NMMA infusion. HOI decreased plasma renin activity and aldosterone and increased plasma atrial natriuretic peptide and urinary cGMP. L-NMMA decreased urinary cGMP, but did not affect the plasma hormones or the changes induced by HOI. L-NMMA decreased the [¹⁵N]-arginine-to-[¹⁵N]-citrulline conversion rate to one-third of baseline. The results indicate that in a state of NO deficiency in humans, the kidney can still respond to an acute volume challenge with vasorelaxation, diuresis, and natriuresis.

This article has been cited by other articles:

				M. Schou, A. Gabrielsen, N. E. Bruun, P. Skott, B. Pump, H. Dige-Petersen, E. Frandsen, P. Bie, J. Warberg, N. J. Christensen, et al. Angiotensin II attenuates the natriuresis of water immersion in humans Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R187 - R196. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673