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

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 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.