Ortiz Pablo, Stoos Barbara A, Hong Nancy J, Boesch Dianne M, Plato Craig F, Garvin Jeffrey L
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202, USA.
Hypertension. 2003 Mar;41(3 Pt 2):682-7. doi: 10.1161/01.HYP.0000047872.07864.20. Epub 2002 Dec 23.
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 micromol/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.
L-精氨酸通过激活内皮型一氧化氮合酶（eNOS）并增加一氧化氮（NO）生成，抑制髓袢升支粗段（THAL）对氯化钠（NaCl）的重吸收。抑制肾脏NO生成并结合高盐饮食会导致高血压，并且THAL与盐敏感性高血压有关。我们推测，高盐饮食会增强L-精氨酸对THAL重吸收NaCl的抑制作用，原因是eNOS表达增加和NO生成增多。为了验证这一点，我们使用了来自正常盐（NS）或高盐饮食（HS）喂养7至10天大鼠的分离THAL。L-精氨酸（1 mmol/L）使HS饮食大鼠的THAL中氯离子重吸收降低了56±10%，但在NS饮食大鼠的THAL中仅降低了29±3%。与NS组相比，HS饮食大鼠分离的THAL中eNOS表达增加了3.9倍（P<0.03）。然而，用DAF-2 DA或NO敏感电极测量发现，L-精氨酸使两组THAL中的NO水平升高到相同程度。为了确定高盐饮食是否会增加THAL对NO的敏感性，我们测试了NO供体亚硝基铁氰化钠对氯离子重吸收的影响。在HS饮食大鼠来源的THAL中，1和5 μmol/L亚硝基铁氰化钠分别使氯离子重吸收降低了35±5%和58±6%。相比之下，相同浓度的亚硝基铁氰化钠在NS饮食大鼠来源的THAL中使氯离子重吸收降低了4±4%（与HS饮食相比P<0.03）和43±9%。我们得出结论，高盐饮食增强了THAL中NO的作用。尽管eNOS蛋白增加，但高盐饮食并未增强L-精氨酸刺激的NO生成。
