Kopkan Libor, Majid Dewan S A
Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Hypertension. 2006 Mar;47(3):568-72. doi: 10.1161/01.HYP.0000200027.34925.93. Epub 2006 Jan 9.
An enhancement of superoxide (O2-) activity was shown to contribute to the development of hypertension induced by NO deficiency. To better understand the mechanistic role of O2- in this NO-deficient hypertension, we evaluated the renal responses to acute intraarterial administration of an O2- scavenger, tempol (50 microg/min per 100 g of body weight) in anesthetized male Sprague-Dawley rats treated with NO synthase inhibitor nitro-L-arginine methyl ester (15 mg/kg per day in drinking water, n=7) for 4 weeks, which caused increases in mean arterial pressure (146+/-3 versus 124+/-2 mm Hg) compared with normotensive control rats (n=6). Hypertensive rats had higher renal vascular resistance (29+/-2 versus 20+/-1 mm Hg/mL per minute per gram), as well as lower renal blood flow (5.2+/-0.3 versus 6.3+/-0.2 mL/min per gram; cortical blood flow, 153+/-13 versus 191+/-8 perfusion units; medullary blood flow, 43+/-2 versus 51+/-3 perfusion units) and glomerular filtration rate (0.69+/-0.04 versus 0.90+/-0.05 mL/min per gram) without a significant difference in urinary sodium excretion (0.81+/-0.07 versus 0.86+/-0.12 micromol/min per gram) compared with normotensive rats. Urinary 8-isoprostane excretion rate (6.8+/-0.7 versus 4.5+/-0.3 pg/min per gram) was higher in hypertensive than normotensive rats. Intraarterial infusion of tempol did not alter renal function in normotensive rats. However, tempol significantly decreased renal vascular resistance by 12+/-2% and urinary 8-isoprostane excretion rate by 24+/-4% and increased renal blood flow by 10+/-2%, cortical blood flow by 9+/-2%, medullary blood flow by 15+/-6%, glomerular filtration rate by 11+/-3%, and urinary sodium excretion by 19+/-5% in hypertensive rats. These data indicate that enhanced O2- activity modulates renal hemodynamics and excretory function during reduced NO production and, thus, contributes to the pathophysiology of the NO-deficient form of hypertension.
超氧化物（O2-）活性增强被证明与一氧化氮缺乏诱导的高血压发展有关。为了更好地理解O2-在这种一氧化氮缺乏性高血压中的机制作用，我们评估了在经一氧化氮合酶抑制剂硝基-L-精氨酸甲酯（每天15毫克/千克，饮用水给药，n = 7）处理4周的麻醉雄性Sprague-Dawley大鼠中，急性动脉内给予O2-清除剂tempol（每100克体重50微克/分钟）后的肾脏反应，与正常血压对照大鼠（n = 6）相比，这导致平均动脉压升高（146±3对124±2毫米汞柱）。高血压大鼠的肾血管阻力更高（29±2对20±1毫米汞柱/毫升每分钟每克），肾血流量更低（5.2±0.3对6.3±0.2毫升/分钟每克；皮质血流量，153±13对191±8灌注单位；髓质血流量，43±2对51±3灌注单位）以及肾小球滤过率更低（0.69±0.04对0.90±0.05毫升/分钟每克），与正常血压大鼠相比，尿钠排泄无显著差异（0.81±0.07对0.86±0.12微摩尔/分钟每克）。高血压大鼠的尿8-异前列腺素排泄率（6.8±0.7对4.5±0.3皮克/分钟每克）高于正常血压大鼠。动脉内输注tempol对正常血压大鼠的肾功能无影响。然而，tempol可使高血压大鼠的肾血管阻力显著降低12±2%以及尿8-异前列腺素排泄率降低24±4%，并使肾血流量增加10±2%，皮质血流量增加9±2%，髓质血流量增加15±6%，肾小球滤过率增加11±3%，尿钠排泄增加19±5%。这些数据表明，在一氧化氮生成减少期间，增强的O2-活性调节肾脏血流动力学和排泄功能，因此，有助于一氧化氮缺乏型高血压的病理生理学过程。
