Angiotensin II exerts a cardinal role in the pathogenesis of hypertension and renal injury via action of angiotensin II type 1 (AT₁) receptors. Local renin-angiotensin system (RAS) activity is essential for the mechanisms mediating pathophysiological functions. Proximal tubular angiotensinogen and tubular AT₁ receptors are augmented by intrarenal angiotensin II. Caveolin 1 plays an important role as a regulatory molecule for the compartmentalization of redox signaling events through angiotensin II–induced NADPH oxidase activation in the kidney. A role for the renin-angiotensin system in the development and/or maintenance of hypertension has been demonstrated in spontaneously hypertensive rats (SHRs). Many effects of angiotensin II are dependent on the AT₁ stimulation of reactive oxygen species (ROS) production by NADPH oxidase. Angiotensin II upregulation stimulates oxidative stress in proximal tubules from SHR. The NADPH oxidase 4 (Nox4) is abundantly expressed in kidney proximal tubule cells. Induction of the stress response includes synthesis of heat shock protein 70, a molecular chaperone that has a critical role in the recovery of cells from stress and in cytoprotection, guarding cells from subsequent insults. HSP70 chaperones function in part by driving the molecular triage decision, which determines whether proteins enter the productive folding pathway or result in client substrate ubiquitination and proteasomal degradation. This review examines regulation of losartan-mediated antioxidative stress responses by the chaperone HSP70 in proximal tubule cells of spontaneously hypertensive rats.

中文翻译：

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氯沙坦的肾脏抗氧化作用涉及近曲小管细胞中的热休克蛋白70。


血管紧张素 II 通过血管紧张素 II 1 型 (AT ₁ ) 受体的作用在高血压和肾损伤的发病机制中发挥重要作用。局部肾素-血管紧张素系统（RAS）活性对于介导病理生理功能的机制至关重要。肾内血管紧张素 II 增强近端肾小管血管紧张素原和肾小管 AT ₁受体。 Caveolin 1 作为一种调节分子，通过血管紧张素 II 诱导的肾脏 NADPH 氧化酶激活来划分氧化还原信号事件，发挥着重要作用。肾素-血管紧张素系统在高血压发生和/或维持中的作用已在自发性高血压大鼠（SHR）中得到证实。血管紧张素 II 的许多作用依赖于 AT ₁刺激 NADPH 氧化酶产生活性氧 (ROS ) 。血管紧张素 II 上调会刺激 SHR 近端肾小管的氧化应激。 NADPH 氧化酶 4 (Nox4) 在肾近曲小管细胞中大量表达。应激反应的诱导包括热休克蛋白 70 的合成，热休克蛋白 70 是一种分子伴侣，在细胞从应激中恢复以及细胞保护、保护细胞免受后续损伤方面发挥着关键作用。 HSP70 分子伴侣的部分功能是通过驱动分子分类决策来发挥作用，分子分类决策决定蛋白质是否进入生产性折叠途径或导致客户底物泛素化和蛋白酶体降解。本综述探讨了自发性高血压大鼠近曲小管细胞中分子伴侣 HSP70 对氯沙坦介导的抗氧化应激反应的调节。