Wilcox C S, Deng X, Welch W J
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Am J Physiol. 1998 Jun;274(6):R1588-93. doi: 10.1152/ajpregu.1998.274.6.R1588.
Micropuncture studies of single nephrons have shown that macula densa solute reabsorption via a furosemide-sensitive pathway activates nitric oxide (NO) generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt loading. We investigated the hypothesis that changes in NO generation via nNOS in the macula densa contribute to changes in whole kidney NO generation and action during alterations in salt intake. Groups of rats (n = 6-10) were equilibrated to high-salt (HS) or low-salt (LS) diets and were administered a vehicle (Veh), 7-nitroindazole (7-NI; a relatively selective inhibitor of nNOS), or furosemide (F; an inhibitor of macula densa solute reabsorption) with volume replacement. Compared with LS, excretion of the NO metabolites, NO2 plus NO3 (NOX) was increased during HS (LS: 9.0 +/- 0.5 vs. HS: 15.7 +/- 0.8 micromol/24 h; P < 0.001), but this difference was prevented by 7-NI (LS: 7.4 +/- 1.3 vs. HS: 9.4 +/- 1.6 micromol/24 h; NS). During nonselective blockade of NOS with NG-nitro-L-arginine methyl ester (L-NAME), renal vascular resistance (RVR) increased more in HS than LS (HS: +160 +/- 17 vs. LS: +83 +/- 10%; P < 0.001). This difference in response to nonselective NOS inhibition was prevented by pretreatment with 7-NI (HS: +28 +/- 6 vs. LS: +34 +/- 8%; NS) or F with volume replacement (HS: +79 +/- 11 vs. LS: +62 +/- 4%; NS). In conclusion, compared with salt restriction, HS intake increases NO generation and renal action that depend on nNOS and macula densa solute reabsorption.
对单个肾单位的微穿刺研究表明，致密斑通过速尿敏感途径进行的溶质重吸收可通过神经元型一氧化氮合酶（nNOS）激活一氧化氮（NO）的生成。在盐负荷增加时，该途径会增强。我们研究了以下假说：在盐摄入量改变期间，致密斑中通过nNOS生成的NO的变化会导致全肾NO生成及作用的改变。将大鼠分组（n = 6 - 10），使其适应高盐（HS）或低盐（LS）饮食，并给予溶媒（Veh）、7-硝基吲唑（7-NI；一种相对选择性的nNOS抑制剂）或速尿（F；致密斑溶质重吸收抑制剂）并补充液体。与LS组相比，HS组中NO代谢产物NO2加NO3（NOX）的排泄增加（LS组：9.0±0.5 vs. HS组：15.7±0.8微摩尔/24小时；P < 0.001），但7-NI可消除这种差异（LS组：7.4±1.3 vs. HS组：9.4±1.6微摩尔/24小时；无显著性差异）。在用NG-硝基-L-精氨酸甲酯（L-NAME）非选择性阻断一氧化氮合酶期间，HS组肾血管阻力（RVR）的增加幅度大于LS组（HS组：+160±17 vs. LS组：+83±10%；P < 0.001）。用7-NI预处理（HS组：+28±6 vs. LS组：+34±8%；无显著性差异）或补充液体的F预处理（HS组：+79±11 vs. LS组：+62±4%；无显著性差异）可消除对非选择性一氧化氮合酶抑制反应的这种差异。总之，与限盐相比，高盐摄入会增加依赖于nNOS和致密斑溶质重吸收的NO生成及肾脏作用。
