Haque Mohammed Z, Majid Dewan S A
Department of Physiology, Tulane University Health Sciences Center, New Orleans, La 70112, USA.
Hypertension. 2004 Feb;43(2):335-40. doi: 10.1161/01.HYP.0000111137.15873.4a. Epub 2004 Jan 12.
To determine the role of endogenous superoxide (O2-) in the kidney, we assessed renal hemodynamics and excretory function in gp91(PHOX) (a NAD(P)H oxidase subunit) gene knockout (KO) mice and compared these findings with those of wild-type (WT) strain C57BL/6 mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances respectively in anesthetized mice (n=8 in each group). There were higher baseline RBF (4.3+/-0.4 versus 2.5+/-0.2 mL/min per gram; P<0.002) and lower renal vascular resistance (RVR) (16+/-1.4 versus 29+/-2.3 mm Hg/mL/min per gram; P<0.0001) in KO compared with WT without a significant difference in mean arterial pressure (MAP) (67+/-2 versus 71+/-2 mm Hg) and GFR (0.66+/-0.09 versus 0.73+/-0.05 mL/min per gram) between the strains. Intravenous infusion of angiotensin II (Ang II) (2 ng/min per gram of body weight) for 30 minutes caused a lesser degree of decreases in RBF (-8% versus -33%) and of increases in RVR (+73% versus +173%) in KO compared with WT. GFR was increased (43%) in KO but not in WT during Ang II infusion. Urinary excretion of nitrate/nitrite was higher in conscious KO (n=5) than in WT (n=5), indicating an increase in nitric oxide bioavailability that could be the cause of high RBF and low RVR in KO. These data indicate that gp91(PHOX), a subunit of NAD(P)H oxidase, plays a regulatory role in the maintenance of renal vascular tone. These results also suggest that the mechanism of Ang II-mediated renal vascular action involves concomitant generation of O2-.
为了确定内源性超氧化物（O2-）在肾脏中的作用，我们评估了gp91（PHOX）（一种NAD（P）H氧化酶亚基）基因敲除（KO）小鼠的肾脏血流动力学和排泄功能，并将这些结果与野生型（WT）C57BL/6小鼠的结果进行比较。分别通过对麻醉小鼠（每组n = 8）的对氨基马尿酸（PAH）清除率和菊粉清除率来测定肾血流量（RBF）和肾小球滤过率（GFR）。与WT相比，KO小鼠的基线RBF较高（4.3±0.4对2.5±0.2 mL/分钟/克；P<0.002），肾血管阻力（RVR）较低（16±1.4对29±2.3 mmHg/mL/分钟/克；P<0.0001），而两品系之间的平均动脉压（MAP）（67±2对71±2 mmHg）和GFR（0.66±0.09对0.73±0.05 mL/分钟/克）无显著差异。静脉输注血管紧张素II（Ang II）（2 ng/分钟/克体重）30分钟后，与WT相比，KO小鼠的RBF降低程度较小（-8%对-33%），RVR升高程度较小（+73%对+173%）。在输注Ang II期间，KO小鼠的GFR升高（43%），而WT小鼠则未升高。清醒的KO小鼠（n = 5）的尿硝酸盐/亚硝酸盐排泄量高于WT小鼠（n = 5），表明一氧化氮生物利用度增加，这可能是KO小鼠RBF高和RVR低的原因。这些数据表明，NAD（P）H氧化酶的亚基gp91（PHOX）在维持肾血管张力中起调节作用。这些结果还表明，Ang II介导的肾血管作用机制涉及O2-的同时生成。
