肾内血管紧张素II与Dahl盐敏感性高血压中的炎症、肾损伤及功能障碍相关。
Intrarenal Angiotensin ii is associated with inflammation, renal damage and dysfunction in dahl salt-sensitive hypertension.
作者信息
Lin L, Phillips W E, Manning R D
机构信息
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
出版信息
J Am Soc Hypertens. 2009 Sep-Oct;3(5):306-14. doi: 10.1016/j.jash.2009.08.002.
BACKGROUND
The goal of this study was to test the hypothesis that intrarenal Ang II has a proinflammatory effect leading to renal damage and dysfunction in Dahl S rats on high Na intake.
METHODS
Forty-six 7-to 8-week old Dahl S or R/Rapp strain rats were maintained for 5 weeks on high sodium (8%) with or without candesartan cilexetil in daily doses of 10-15 mg/kg/day. Arterial catheters were implanted at day 28.
RESULTS
By day 35 in the high Na S + candesartan rats, renal tissue Ang II concentration, renal monocytes/macrophages, TNFalpha, and MCP-1 significantly decreased. Plasma Ang II remained at very low levels in all groups. Reduced renal damage in candesartan-treated Dahl S rats was demonstrated by marked decreases in urinary protein excretion and renal glomerular and interstitial damage. After 5 weeks of high Na, compared to high Na Dahl S rats, arterial pressure was unchanged in candesartan S rats, but creatinine clearance was increased.
CONCLUSIONS
Therefore, candesartan reduced renal tissue Ang II, renal damage, infiltration of immune cells, cytokines, chemokines, and improved renal hemodynamics. These data suggest that intrarenal Ang II plays an important role in causing renal inflammation which leads to renal cortical damage, proteinuria, and decreases in renal hemodynamics.
背景
本研究的目的是验证以下假设：在高钠摄入的 Dahl S 大鼠中，肾内血管紧张素 II（Ang II）具有促炎作用，可导致肾损伤和功能障碍。
方法
46 只 7 至 8 周龄的 Dahl S 或 R/Rapp 品系大鼠，在高钠（8%）饮食条件下饲养 5 周，部分大鼠每日给予坎地沙坦酯，剂量为 10 - 15 mg/kg/天。在第 28 天植入动脉导管。
结果
在高钠饮食的 Dahl S + 坎地沙坦大鼠中，至第 35 天时，肾组织 Ang II 浓度、肾单核细胞/巨噬细胞、肿瘤坏死因子α（TNFα）和单核细胞趋化蛋白 - 1（MCP - 1）显著降低。所有组的血浆 Ang II 水平均维持在极低水平。坎地沙坦治疗的 Dahl S 大鼠肾损伤减轻，表现为尿蛋白排泄、肾小球和间质损伤明显减少。高钠饮食 5 周后，与高钠 Dahl S 大鼠相比，坎地沙坦治疗的 Dahl S 大鼠动脉血压未改变，但肌酐清除率增加。
结论
因此，坎地沙坦降低了肾组织 Ang II 水平、肾损伤、免疫细胞浸润、细胞因子和趋化因子，并改善了肾血流动力学。这些数据表明，肾内 Ang II 在引发肾炎症中起重要作用，进而导致肾皮质损伤、蛋白尿和肾血流动力学降低。
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