Guron Gregor S, Grimberg Elisabeth S, Basu Samar, Herlitz Hans
Department of Nephrology, Institute of Internal Medicine, Göteborg, Sweden.
J Hypertens. 2006 Feb;24(2):387-94. doi: 10.1097/01.hjh.0000200511.02700.99.
To investigate the acute effects of the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) on split kidney function, and renal haemodynamics, in two-kidney, one-clip (2K1C) hypertensive rats.
Three weeks after clipping, or the sham procedure, the effects of intravenous tempol (200 micromol/kg per h) were evaluated on thiobutabarbital anaesthetized Sprague-Dawley rats.
Mean arterial pressure (MAP; 152 +/- 3 versus 122 +/- 3 mmHg, P < 0.001), plasma renin activity (28.7 +/- 3.0 versus 9.5 +/- 0.6 ng/ml per h, P < 0.001) and urinary 8-iso-prostaglandin F2alpha excretion (124 +/- 4 versus 92 +/- 10 pmol/24 h, P = 0.003) were significantly elevated in 2K1C rats compared with sham. Tempol reduced MAP by 15 +/- 1% compared with baseline (P < 0.001) in 2K1C rats. In clipped kidneys, tempol increased the glomerular filtration rate (GFR; +50 +/- 15% from baseline) and the effective renal plasma flow (ERPF; +37 +/- 13%, from baseline), and reduced renal vascular resistance (RVR; -32 +/- 6% from baseline) compared with saline-treated controls (P < 0.05). In non-clipped kidneys, tempol reduced RVR (-24 +/- 5% from baseline) compared with saline-treated controls (P = 0.001). In sham-operated rats, tempol produced a modest reduction in MAP (-8 +/- 2% from baseline, P = 0.003), but did not significantly affect renal haemodynamics or function.
Tempol reduced MAP and RVR in both clipped and non-clipped kidneys of 2K1C hypertensive rats. In addition, tempol increased ERPF and GFR in the clipped kidney. These findings suggest important roles for superoxide in the regulation of renal haemodynamics during the early maintenance phase of renovascular hypertension.
研究超氧化物歧化酶模拟物4-羟基-2,2,6,6-四甲基哌啶-1-氧基（tempol）对二肾一夹（2K1C）高血压大鼠分肾功能及肾血流动力学的急性影响。
夹闭或假手术3周后，评估静脉注射tempol（200微摩尔/千克每小时）对硫喷妥钠麻醉的Sprague-Dawley大鼠的影响。
与假手术组相比，2K1C大鼠的平均动脉压（MAP；152±3对122±3毫米汞柱，P<0.001）、血浆肾素活性（28.7±3.0对9.5±0.6纳克/毫升每小时，P<0.001）和尿8-异前列腺素F2α排泄量（124±4对92±10皮摩尔/24小时，P = 0.003）显著升高。与基线相比，tempol使2K1C大鼠的MAP降低了15±1%（P<0.001）。在夹闭的肾脏中，与生理盐水处理的对照组相比，tempol使肾小球滤过率（GFR；较基线增加50±15%）和有效肾血浆流量（ERPF；较基线增加37±13%）增加，并降低了肾血管阻力（RVR；较基线降低32±6%）（P<0.05）。在未夹闭的肾脏中，与生理盐水处理的对照组相比，tempol使RVR降低（较基线降低24±5%）（P = 0.001）。在假手术大鼠中，tempol使MAP适度降低（较基线降低8±2%，P = 0.003），但对肾血流动力学或功能无显著影响。
Tempol降低了2K1C高血压大鼠夹闭和未夹闭肾脏的MAP和RVR。此外，tempol增加了夹闭肾脏的ERPF和GFR。这些发现表明超氧化物在肾血管性高血压早期维持阶段肾血流动力学调节中起重要作用。
