This Article Full Text Full Text (PDF) Data Supplement 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 Citation Map 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. Related Collections Cardio-renal physiology/pathophysiology

(Hypertension. 2003;41:682.)
© 2003 American Heart Association, Inc.

Scientific Contributions

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; Jeffrey L. Garvin

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

Correspondence to Dr Pablo Ortiz, Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202. E-mail portiz1{at}hfhs.org

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

This article has been cited by other articles:

				M. Herrera, P. A. Ortiz, and J. L. Garvin Regulation of thick ascending limb transport: role of nitric oxide Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1279 - F1284. [Abstract] [Full Text] [PDF]

				M. Herrera, G. Silva, and J. L. Garvin A High-Salt Diet Dissociates NO Synthase-3 Expression and NO Production by the Thick Ascending Limb Hypertension, January 1, 2006; 47(1): 95 - 101. [Abstract] [Full Text] [PDF]

				M. Herrera and J. L. Garvin A high-salt diet stimulates thick ascending limb eNOS expression by raising medullary osmolality and increasing release of endothelin-1 Am J Physiol Renal Physiol, January 1, 2005; 288(1): F58 - F64. [Abstract] [Full Text] [PDF]

				M. Varela, M. Herrera, and J. L. Garvin Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2- and is diminished by a high-salt diet Am J Physiol Renal Physiol, August 1, 2004; 287(2): F224 - F230. [Abstract] [Full Text] [PDF]

				M. Herrera and J. L. Garvin Endothelin stimulates endothelial nitric oxide synthase expression in the thick ascending limb Am J Physiol Renal Physiol, August 1, 2004; 287(2): F231 - F235. [Abstract] [Full Text] [PDF]

				P. A. Ortiz, N. J. Hong, and J. L. Garvin Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. II. Role of PI3-kinase and Hsp90 Am J Physiol Renal Physiol, August 1, 2004; 287(2): F281 - F288. [Abstract] [Full Text] [PDF]

				D. W. Jones Dietary Sodium and Blood Pressure Hypertension, May 1, 2004; 43(5): 932 - 935. [Full Text] [PDF]

				P. A. Ortiz, N. J. Hong, D. Wang, and J. L. Garvin Gene Transfer of eNOS to the Thick Ascending Limb of eNOS-KO Mice Restores the Effects of L-Arginine on NaCl Absorption Hypertension, October 1, 2003; 42(4): 674 - 679. [Abstract] [Full Text] [PDF]