Defective fluid and HCO(3)(-) absorption in proximal tubule of neuronal nitric oxide synthase-knockout mice.
Defective fluid and HCO(3)(-) absorption in proximal tubule of neuronal nitric oxide synthase-knockout mice.
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DOI：
10.1152/ajprenal.2000.279.3.f518
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发表时间：
2000-09
期刊：
影响因子：
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通讯作者：
Tong Wang;Fiona M. Inglis;Robert G. Kalb
中科院分区：
文献类型：
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作者：
Tong Wang;Fiona M. Inglis;Robert G. Kalb
利用肾清除技术和近端小管原位微灌注，我们研究了N（G）-单甲基-L-精氨酸甲酯（L-NAME）对野生型小鼠液体和HCO（3）（-）转运的影响，并研究了神经元型一氧化氮合酶（nNOS）基因敲除小鼠近端小管转运。在野生型小鼠中，给予L-NAME（3 mg/kg静脉推注）显著增加平均血压、尿量和尿Na（+）排泄。静脉推注L-NAME并加入管腔灌注液中，可减少近端小管中液体（60%）和HCO（3）（-）（49%）的吸收。在nNOS基因敲除小鼠中，HCO（3）（-）的尿排泄量显著高于野生型小鼠（3.12 +/- 0.52 vs. 1。40 +/- 0.33 mM），HCO（3）（-）和液体吸收率分别降低62%和72%。动脉血HCO（3）（-）浓度（20.7与25.7 mM）和血液pH值（7.27与7.34）均较低，表明nNOS敲除小鼠存在显著的代谢性酸中毒。nNOS敲除小鼠的血压（76.2 +/- 4.6 mmHg）低于野生型对照动物（102.9 +/- 8.4 mmHg）;然而，它对L-NAME的反应（125.5 +/- 5.07 mmHg）有所增加。血浆Na（+）和K（+）与对照值无显著差异。我们的数据表明，HCO（3）（-）和近端小管中的液体吸收的大部分是由nNOS控制的。缺乏这种同工酶的小鼠在近端小管中的液体和HCO（3）（-）吸收方面存在缺陷，并发生代谢性酸中毒，这表明nNOS在调节酸碱平衡中起重要作用。
Using renal clearance techniques and in situ microperfusion of proximal tubules, we examined the effects of N(G)-monomethyl-L-arginine methyl ester (L-NAME) on fluid and HCO(3)(-) transport in wild-type mice and also investigated proximal tubule transport in neuronal nitric oxide synthase (nNOS)-knockout mice. In wild-type mice, administration of L-NAME (3 mg/kg bolus iv) significantly increased mean blood pressure, urine volume, and urinary Na(+) excretion. L-NAME, given by intravenous bolus and added to the luminal perfusion solution, decreased absorption of fluid (60%) and HCO(3)(-) (49%) in the proximal tubule. In nNOS-knockout mice, the urinary excretion of HCO(3)(-) was significantly higher than in the wild-type mice (3.12 +/- 0.52 vs. 1. 40 +/- 0.33 mM) and the rates of HCO(3)(-) and fluid absorption were 62 and 72% lower, respectively. Both arterial blood HCO(3)(-) concentration (20.7 vs. 25.7 mM) and blood pH (7.27 vs. 7.34) were lower, indicating a significant metabolic acidosis in nNOS-knockout mice. Blood pressure was lower in nNOS-knockout mice (76.2 +/- 4.6 mmHg) than in wild-type control animals (102.9 +/- 8.4 mmHg); however, it increased in response to L-NAME (125.5 +/- 5.07 mmHg). Plasma Na(+) and K(+) were not significantly different from control values. Our data show that a large component of HCO(3)(-) and fluid absorption in the proximal tubule is controlled by nNOS. Mice without this isozyme are defective in absorption of fluid and HCO(3)(-) in the proximal tubule and develop metabolic acidosis, suggesting that nNOS plays an important role in the regulation of acid-base balance.