Lerman L O, Nath K A, Rodriguez-Porcel M, Krier J D, Schwartz R S, Napoli C, Romero J C
Department of Internal Medicine, Division of Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Hypertension. 2001 Feb;37(2 Pt 2):541-6. doi: 10.1161/01.hyp.37.2.541.
The pathophysiological mechanisms responsible for maintenance of chronic renovascular hypertension remain undefined. Excess angiotensin II generation may lead to release of reactive oxygen species and increased vasoconstrictor activity. To examine the potential involvement of oxidation-sensitive mechanisms in the pathophysiology of renovascular hypertension, blood samples were collected and renal blood flow measured with electron-beam computed tomography in pigs 5 and 10 weeks after induction of unilateral renal artery stenosis (n=7) or sham operation (n=7). Five weeks after procedure, plasma renin activity and mean arterial pressure were elevated in hypertensive pigs. Levels of prostaglandin F2alpha (PGF(2alpha))-isoprostanes, vasoconstrictors and markers of oxidative stress, also were significantly increased (157+/-21 versus 99+/-16 pg/mL; P<0.05) and correlated with both plasma renin activity (r=0.83) and arterial pressure (r=0.82). By 10 weeks, plasma renin activity returned to baseline but arterial pressure remained elevated (144+/-10 versus 115+/-5 mm Hg; P:<0.05). Isoprostane levels remained high and still correlated directly with the increase in arterial pressure (r=0.7) but not with plasma renin activity. Stenotic kidney blood flow was decreased at both studies. In shock-frozen cortical tissue, ex vivo endogenous intracellular radical scavengers were significantly decreased in both kidneys. The present study demonstrates, for the first time, that in early renovascular hypertension, an increase in plasma renin activity and arterial pressure is associated with increased systemic oxidative stress. When plasma renin activity later declines, PGF(2alpha)-isoprostanes remain elevated, possibly due to local activation or slow responses to angiotensin II, and may participate in sustenance of arterial pressure. Moreover, oxidation-sensitive mechanisms may influence ischemic and hypertensive parenchymal renal injury.
导致慢性肾血管性高血压持续存在的病理生理机制仍不明确。血管紧张素II生成过多可能导致活性氧的释放和血管收缩活性增加。为了研究氧化敏感机制在肾血管性高血压病理生理学中的潜在作用，在诱导单侧肾动脉狭窄（n = 7）或假手术（n = 7）后5周和10周，采集猪的血样并用电子束计算机断层扫描测量肾血流量。手术后5周，高血压猪的血浆肾素活性和平均动脉压升高。前列腺素F2α（PGF(2α)）-异前列腺素、血管收缩剂和氧化应激标志物的水平也显著升高（157±21对99±16 pg/mL；P<0.05），并与血浆肾素活性（r = 0.83）和动脉压（r = 0.82）相关。到10周时，血浆肾素活性恢复到基线，但动脉压仍升高（144±10对115±5 mmHg；P<0.05）。异前列腺素水平仍然很高，并且仍与动脉压升高直接相关（r = 0.7），但与血浆肾素活性无关。在两项研究中，狭窄肾脏的血流量均减少。在休克冷冻的皮质组织中，两个肾脏的离体内源性细胞内自由基清除剂均显著减少。本研究首次证明，在早期肾血管性高血压中，血浆肾素活性和动脉压的升高与全身氧化应激增加有关。当血浆肾素活性随后下降时，PGF(2α)-异前列腺素仍升高，可能是由于局部激活或对血管紧张素II的缓慢反应，并可能参与动脉压的维持。此外，氧化敏感机制可能影响缺血性和高血压性肾实质损伤。
