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

2003; Lippincott Williams & Wilkins; Volume: 41; Issue: 3 Linguagem: Inglês

10.1161/01.hyp.0000047872.07864.20

1524-4563

Pablo A. Ortiz, Barbara A. Stoos, Nancy J. Hong, Dianne M. Boesch, Craig F. Plato, Jeffrey L. Garvin,

Sodium Intake and Health

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.