Barton C H, Ni Z, Vaziri N D
Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, California, USA.
Kidney Int. 2001 Sep;60(3):1083-7. doi: 10.1046/j.1523-1755.2001.0600031083.x.
Abdominal aortic coarctation above the renal arteries leads to severe hypertension (HTN) above the stenotic site. We have recently shown marked up-regulations of endothelial nitric oxide synthase (eNOS) in heart and thoracic aorta and of neuronal NOS (nNOS) in the brain of rats with severe aortic coarctation above the renal arteries. We hypothesize that the presence of severe regional HTN in the face of marked up-regulation of NO system may be partly due to enhanced NO inactivation by reactive oxygen species (ROS) leading to functional NO deficiency.
Tissue nitrotyrosine (which is the footprint of NO interaction with ROS) was determined by Western blot in sham-operated control and aortic-banded (above renal arteries) rats three weeks postoperatively. Intra-arterial pressure and tissue nitrotyrosine (Western blot) were measured.
The banded group showed a marked rise in arterial pressure measured directly through a carotid cannula (203 +/- 9 vs. 131 +/- 2 mm Hg, P < 0.01). Compared with the sham-operated controls, the banded animals exhibited significant increases in nitrotyrosine abundance in the heart, brain, and the aorta segment above the stricture. In contrast, nitrotyrosine abundance was unchanged in the abdominal aorta segment below the stricture wherein blood pressure was not elevated.
Coarctation-induced HTN is associated with increased nitrotyrosine abundance in all tissues exposed to high arterial pressure, denoting enhanced ROS-mediated inactivation and sequestration of NO in these sites. This can, in part, account for severe regional HTN in this model. The normality of nitrotyrosine abundance in the abdominal aorta wherein blood pressure is not elevated points to the role of baromechanical factors as opposed to circulating humoral factors that were necessarily similar in both segments.
肾动脉上方的腹主动脉缩窄会导致缩窄部位上方出现严重高血压（HTN）。我们最近发现，肾动脉上方严重主动脉缩窄的大鼠心脏和胸主动脉中内皮型一氧化氮合酶（eNOS）以及大脑中神经元型一氧化氮合酶（nNOS）显著上调。我们推测，在一氧化氮系统显著上调的情况下出现严重局部高血压，可能部分是由于活性氧（ROS）增强了一氧化氮的失活，导致功能性一氧化氮缺乏。
通过蛋白质免疫印迹法测定假手术对照大鼠和主动脉缩窄（肾动脉上方）大鼠术后三周组织中的硝基酪氨酸（这是一氧化氮与活性氧相互作用的标志）。测量动脉内压力和组织硝基酪氨酸（蛋白质免疫印迹法）。
缩窄组通过颈动脉插管直接测量的动脉压显著升高（203±9 vs. 131±2 mmHg，P<0.01）。与假手术对照组相比，缩窄动物心脏、大脑和缩窄上方主动脉段的硝基酪氨酸丰度显著增加。相比之下，缩窄下方腹主动脉段的硝基酪氨酸丰度未发生变化，该部位血压未升高。
缩窄诱导的高血压与所有暴露于高动脉压的组织中硝基酪氨酸丰度增加有关，表明这些部位活性氧介导的一氧化氮失活和隔离增强。这可以部分解释该模型中的严重局部高血压。血压未升高的腹主动脉段硝基酪氨酸丰度正常，表明压力机械因素起作用，而非循环体液因素，这两个部位的循环体液因素必然相似。
