Division of Nephrology and Hypertension, Hypertension, Kidney, and Vascular Center, and Angiogenesis Program of the Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
Hypertension. 2010 Feb;55(2):298-304. doi: 10.1161/HYPERTENSIONAHA.109.135426. Epub 2010 Jan 4.
Angiotensin II maintains renal cortical blood flow and renal oxygenation in the clipped kidney of early 2-kidney, 1-clip Goldblatt hypertensive (2K,1C) rats. The involvement of Ang II is believed to decline, whereas oxidative stress increases during the progression of 2K,1C hypertension. We investigated the hypothesis that the acute administration of drugs to inhibit reactive oxygen species (Tempol), angiotensin II type 1 receptors (candesartan), or angiotensin-converting enzyme (enalaprilat) lowers mean arterial pressure and increases kidney blood flow and oxygenation in the clipped kidney of chronic 2K,1C rats in contrast to sham controls. Twelve months after left renal artery clipping or sham, mean arterial pressure, renal cortical blood flow, and renal cortical and medullary oxygen tension were measured after acute administration of Tempol followed by enalaprilat or candesartan followed by enalaprilat. The mean arterial pressure of the 2K,1C rat was reduced by candesartan (-9%) and, more effectively, by Tempol (-35%). All of the applied treatments had similar blood pressure-lowering effects in sham rats (average: -21%). Only Tempol increased cortical blood flow (+35%) and cortical and medullary oxygen tensions (+17% and +94%, respectively) in clipped kidneys of 2K,1C rats. Administration of enalaprilat had no additional effect, except for a modest reduction in cortical blood flow in the clipped kidney of 2K,1C rats when coadministered with candesartan (-10%). In conclusion, acute administration of Tempol is more effective than candesartan in reducing the mean arterial blood pressure and improving renal blood perfusion and oxygenation in the clipped kidney of chronic 2K,1C rats.
血管紧张素 II 维持早期 2 肾 1 夹 Goldblatt 高血压(2K,1C)大鼠夹闭肾皮质血流和氧合。在 2K,1C 高血压的进展过程中,认为血管紧张素 II 的作用下降,而氧化应激增加。我们假设,急性给予药物抑制活性氧(Tempol)、血管紧张素 II 型 1 受体(坎地沙坦)或血管紧张素转换酶(依那普利拉),可以降低慢性 2K,1C 大鼠夹闭肾的平均动脉压,增加夹闭肾的血流和氧合,与假手术对照相比。在左肾动脉夹闭或假手术后 12 个月,急性给予 Tempol 后给予依那普利拉或坎地沙坦后给予依那普利拉,测量平均动脉压、肾皮质血流以及肾皮质和髓质氧张力。2K,1C 大鼠的平均动脉压被坎地沙坦(-9%)和更有效地被 Tempol(-35%)降低。所有应用的治疗在假手术大鼠中均具有相似的降压作用(平均:-21%)。只有 Tempol 增加了夹闭肾的皮质血流(+35%)和皮质及髓质氧张力(分别增加 17%和 94%)。依那普利拉的给药没有额外的作用,除了当与坎地沙坦联合给药时,2K,1C 大鼠夹闭肾的皮质血流略有减少(-10%)。总之,急性给予 Tempol 比坎地沙坦更有效地降低慢性 2K,1C 大鼠夹闭肾的平均动脉压,并改善肾血流灌注和氧合。