It's been shown that COX-2-dependent activation of renal (pro)renin receptor (PRR) contributes to angiotensin II (AngII)-induced hypertension. However, less is known about the involvement of this mechanism in AngII-independent hypertension. The goal of the present study was to test whether or not COX-2-dependent upregulation of PRR serves as a universal mechanism contributing to AngII-dependent and -independent hypertension. Here we examined the association between renal COX-2 and PRR during deoxycorticosterone acetate (DOCA)-salt hypertension in rats. By immunoblotting and immunofluorescence, renal protein expression of PRR was remarkably upregulated by (DOCA)-salt treatment. Surprisingly, this upregulation of renal PRR expression was unaffected by a COX-2 inhibitor celecoxib. To address the role of renal PRR to pathogenesis of DOCA-salt hypertension, a decoy PRR inhibitor PRO20 was infused to the renal medulla of uninephrectomized Sprague-Dawley rats for 14 days. Radiotelemetry demonstrated effective attenuation of DOCA-salt hypertension by intramedullary infusion of a PRR inhibitor PRO20. In parallel, DOCA-salt-induced hypertrophy in the heart and the kidney, and proteinuria were improved as well, accompanied with blunted polydipsia and polyuria. In contrast, intravenous infusion of PRO20 was less effective in attenuating DOCA-salt-induced hypertension and cardiorenal injury. Together, these results suggest that COX-2-indepdendent activation of renal PRR contributes to DOCA-salt hypertension.

中文翻译：

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肾 (Pro) 肾素受体的 COX-2 独立激活导致大鼠 DOCA-盐高血压。

研究表明，COX-2 依赖性肾素原受体 (PRR) 激活会导致血管紧张素 II (AngII) 诱发的高血压。然而，人们对这种机制在不依赖于血管紧张素II的高血压中的作用知之甚少。本研究的目的是测试 COX-2 依赖性 PRR 上调是否是导致 AngII 依赖性和非依赖性高血压的普遍机制。在这里，我们研究了大鼠醋酸脱氧皮质酮 (DOCA) 盐高血压期间肾脏 COX-2 与 PRR 之间的关联。通过免疫印迹和免疫荧光，（DOCA）盐处理显着上调了 PRR 的肾蛋白表达。令人惊讶的是，这种肾 PRR 表达的上调不受 COX-2 抑制剂塞来昔布的影响。为了阐明肾脏 PRR 在 DOCA 盐高血压发病机制中的作用，将诱饵 PRR 抑制剂 PRO20 注入未切除肾的 Sprague-Dawley 大鼠的肾髓质 14 天。无线电遥测表明，通过髓内输注 PRR 抑制剂 PRO20 可以有效减弱 DOCA 盐高血压。与此同时，DOCA盐引起的心脏和肾脏肥大以及蛋白尿也得到改善，并伴有多饮和多尿减弱。相比之下，静脉输注 PRO20 在减轻 DOCA 盐诱发的高血压和心肾损伤方面效果较差。总之，这些结果表明肾 PRR 的 COX-2 独立激活有助于 DOCA 盐高血压。