Published Online
on December 23, 2002

A more recent version of this article appeared on March 1, 2003

This Article Full Text (PDF) All Versions of this Article: 41/3/682    most recent 01.HYP.0000047872.07864.20v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ortiz, P. Articles by Garvin, J. L. Search for Related Content PubMed PubMed Citation Articles by Ortiz, P. Articles by Garvin, J. L. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ARGININE NITRIC OXIDE SODIUM CHLORIDE Related Collections Cardio-renal physiology/pathophysiology

Submitted on September 30, 2002
Revised on October 16, 2002

High-Salt Diet Increases Sensitivity to NO and eNOS Expression But Not NO Production in THALs

Pablo Ortiz^*; Barbara A. Stoos; Nancy J. Hong; Dianne M. Boesch; Craig F. Plato; and Jeffrey L. Garvin

From the Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Mich.

^* To whom correspondence should be addressed. E-mail: portiz1{at}hfhs.org.

Abstract—L-Arginine inhibits thick ascending limb (THAL) NaCl absorption by activating endothelial NO synthase (eNOS) and increasing NO production. Inhibition of renal NO production combined with a high-salt diet produces hypertension, and the THAL has been implicated in salt-sensitive hypertension. We hypothesized that a high-salt diet enhances the inhibitory action of L-arginine on NaCl absorption by THALs because of increased eNOS expression and NO production. To test this, we used isolated THALs from rats on a normal-salt (NS) or high-salt diet (HS) for 7 to 10 days. L-Arginine (1 mmol/L) decreased chloride absorption by 56±10% in THALs from rats on a HS diet, but only 29±3% in THALs from rats on a NS diet. eNOS expression in isolated THALs from rats on a HS diet was increased by 3.9-fold compared with NS (P<0.03). However, L-arginine increased NO levels to the same extent in THALs from both groups, as measured with DAF-2 DA or a NO-sensitive electrode. To determine whether a HS diet increases the sensitivity of the THAL to NO, we tested the effects of the NO donor spermine NONOate on chloride absorption. In THALs from rats on a HS diet, 1 and 5 µmol/L spermine NONOate reduced chloride absorption by 35±5% and 58±6%, respectively. In contrast, these same concentrations of spermine NONOate reduced chloride absorption by 4±4% (P<0.03 versus HS diet) and 43±9% in THALs from rats on a NS diet. We conclude that a HS diet enhances the effect of NO in the THAL. L-Arginine-stimulated NO production was not enhanced by a HS diet, despite increased eNOS protein.

Key words: urine • hypertension, sodium dependent • Na/K/Cl₂ cotransport • nitric oxide synthase

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