Rodriguez-Iturbe Bernardo, Quiroz Yasmir, Kim Choong H, Vaziri Nosratola D
Renal Service, Hospital Universitario, Universidad del Zulia, Instituto de Investigaciones Biomédicas (INBIOMED) Maracaibo, Venezuela.
Am J Hypertens. 2005 Nov;18(11):1449-56. doi: 10.1016/j.amjhyper.2005.05.034.
Renal tubulointerstitial infiltration of activated T cells and macrophages is invariably present and plays a role in elevation of arterial pressure in nearly all animal models of hypertension (HTN). The role, if any, of elevated renal arterial pressure in the pathogenesis of this inflammatory process is uncertain. Also unclear is whether the cellular infiltration is caused by the local activation of immune cells in the kidney or a consequence of leukocyte activation in the systemic circulation.
We studied activation of peripheral blood leukocytes and cellular infiltration in the kidneys of Sprague-Dawley rats with abdominal aorta coarctation (banding) above renal arteries, which causes severe HTN proximal but not distal to coarctation.
Compared with the sham operated controls, the aorta-banded group exhibited tubulointerstitial accumulation of activated T cells, macrophages, angiotensin-II positive cells, leukocyte function-associated antigen-1 integrin expressing cells, increased nitrotyrosine abundance (a measure of oxidative stress), and increased macrophage chemoattractant protein-1 in the kidneys which are not exposed to HTN in this model. These findings were associated with the activation of the circulating leukocytes in the aorta-banded animals.
Increased baromechanical stress is not a requisite for accumulation of T cells and macrophages in the kidney in the coarctation-induced HTN and possibly in other hypertensive disorders. On the contrary, renal hypoperfusion and the consequent activation of renin-angiotensin system may mediate this process by promoting local induction of chemoattractant and inflammatory cytokines. The observed tubulointerstitial inflammation in this model is associated with leukocyte activation in the systemic circulation.
在几乎所有高血压（HTN）动物模型中，活化T细胞和巨噬细胞的肾小管间质浸润均始终存在，并在动脉血压升高过程中发挥作用。肾动脉压力升高在这种炎症过程的发病机制中所起的作用（如果有）尚不确定。同样不清楚的是，细胞浸润是由肾脏中免疫细胞的局部激活引起的，还是全身循环中白细胞激活的结果。
我们研究了肾动脉上方腹主动脉缩窄（扎带）的Sprague-Dawley大鼠外周血白细胞的激活和肾脏中的细胞浸润，这种缩窄会导致缩窄近端而非远端出现严重高血压。
与假手术对照组相比，主动脉扎带组在该模型中未暴露于高血压的肾脏中，活化T细胞、巨噬细胞、血管紧张素II阳性细胞、表达白细胞功能相关抗原-1整合素的细胞出现肾小管间质积聚，硝基酪氨酸丰度增加（氧化应激的一种衡量指标），巨噬细胞趋化蛋白-1增加。这些发现与主动脉扎带动物循环白细胞的激活有关。
在缩窄诱导的高血压以及可能的其他高血压疾病中，增加的气压机械应力并非肾脏中T细胞和巨噬细胞积聚的必要条件。相反，肾脏灌注不足以及随之而来的肾素-血管紧张素系统激活可能通过促进趋化因子和炎性细胞因子的局部诱导来介导这一过程。在该模型中观察到的肾小管间质炎症与全身循环中白细胞的激活有关。
