Silva Guillermo B, Garvin Jeffrey L
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Hypertension. 2008 Dec;52(6):1091-8. doi: 10.1161/HYPERTENSIONAHA.108.120212. Epub 2008 Nov 10.
Renal medullary superoxide (O(2)(-)) increases in angiotensin (Ang) II-dependent hypertension. O(2)(-) increases thick ascending limb Na transport, but the effect of Ang II-dependent hypertension on the thick ascending limb is unknown. We hypothesized that Ang II-dependent hypertension increases thick ascending limb NaCl transport because of enhanced O(2)(-) production and increased protein kinase C (PKC) alpha activity. We measured the effect of Ang II-dependent hypertension on furosemide-sensitive oxygen consumption (a measure of Na transport), O(2)(-) production, and PKCalpha translocation (a measure of PKCalpha activity) in thick ascending limb suspensions. Ang II-dependent hypertension increased furosemide-sensitive oxygen consumption (26.2+/-1.0% versus 36.6+/-1.2% of total oxygen consumption; P<0.01). O(2)(-) was also increased (1.1+/-0.2 versus 3.2+/-0.5 nmol of O(2)(-)/min per milligram of protein; P<0.03) in thick ascending limbs. Unilateral renal infusion of Tempol decreased O(2)(-) (2.4+/-0.4 versus 1.2+/-0.2 nmol of O(2)(-)/min per milligram of protein; P<0.04) and furosemide-sensitive oxygen consumption (32.8+/-1.3% versus 24.0+/-2.1% of total oxygen consumption; P<0.01) in hypertensive rats. Tempol did not affect O(2)(-) or furosemide-sensitive oxygen consumption in normotensive controls and did not alter systolic blood pressure. Ang II-dependent hypertension increased PKCalpha translocation (5.7+/-0.3 versus 13.8+/-1.4 AU per milligram of protein; P<0.01). Unilateral renal infusion of Tempol reduced PKCalpha translocation (5.0+/-0.9 versus 10.4+/-2.6 AU per milligram of protein; P<0.04) in hypertensive rats. Unilateral renal infusion of the PKCalpha inhibitor Gö6976 reduced furosemide-sensitive oxygen consumption (37.4+/-1.5% versus 25.1+/-1.0% of total oxygen consumption; P<0.01) in hypertensive rats. We conclude that Ang II-dependent hypertension enhances thick ascending limb Na transport-related oxygen consumption by increasing O(2)(-) and PKCalpha activity.
在血管紧张素（Ang）II依赖性高血压中，肾髓质超氧化物（O₂⁻）增加。O₂⁻增加髓袢升支粗段的钠转运，但Ang II依赖性高血压对髓袢升支粗段的影响尚不清楚。我们假设，Ang II依赖性高血压会增加髓袢升支粗段的氯化钠转运，这是由于O₂⁻生成增强和蛋白激酶C（PKC）α活性增加所致。我们测量了Ang II依赖性高血压对髓袢升支粗段悬液中呋塞米敏感性氧消耗（钠转运的一种测量指标）、O₂⁻生成以及PKCα易位（PKCα活性的一种测量指标）的影响。Ang II依赖性高血压增加了呋塞米敏感性氧消耗（分别占总氧消耗的26.2±1.0%和36.6±1.2%；P<0.01）。髓袢升支粗段中的O₂⁻也增加了（分别为1.1±0.2和3.2±0.5 nmol O₂⁻/分钟每毫克蛋白质；P<0.03）。单侧肾脏输注Tempol可降低高血压大鼠的O₂⁻（分别为2.4±0.4和1.2±0.2 nmol O₂⁻/分钟每毫克蛋白质；P<0.04）以及呋塞米敏感性氧消耗（分别占总氧消耗的32.8±1.3%和24.0±2.1%；P<0.01）。Tempol对正常血压对照组的O₂⁻或呋塞米敏感性氧消耗没有影响，也未改变收缩压。Ang II依赖性高血压增加了PKCα易位（分别为5.7±0.3和13.8±1.4 AU每毫克蛋白质；P<0.01）。单侧肾脏输注Tempol可降低高血压大鼠的PKCα易位（分别为5.0±0.9和10.4±2.6 AU每毫克蛋白质；P<0.04）。单侧肾脏输注PKCα抑制剂Gö6976可降低高血压大鼠的呋塞米敏感性氧消耗（分别占总氧消耗的37.4±1.5%和25.1±1.0%；P<
