The complex interplay between cyclooxygenase-2 and angiotensin II in regulating kidney function.
The complex interplay between cyclooxygenase-2 and angiotensin II in regulating kidney function.
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DOI：
10.1097/mnh.0b013e32834d9d75
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发表时间：
2012-01
影响因子：
3.2
通讯作者：
Navar LG
中科院分区：
文献类型：
--
作者：
Green T;Gonzalez AA;Mitchell KD;Navar LG
环氧化酶-2 （COX-2）在调节血管紧张素II （Ang II）的有害作用中起关键作用，其中存在肾素-血管紧张素系统（RAS）的不适当激活。这篇综述讨论了COX-2调节激活的RAS对肾功能和血压影响的复杂相互作用的最新进展。正常大鼠COX-2活性升高，但由于钠限制或血管紧张素转换酶（ACE）抑制剂的慢性治疗，肾内Ang II活性不同，对COX-2选择性抑制（尼美舒利）的反应相似，表明不依赖于肾内Ang II活性。依赖于COX-2的髓质血流维持是一致的，不依赖于膳食盐或ACE抑制。相反，COX-2对钠排泄的影响取决于普遍的RAS活性。在慢性高血压模型中，COX-2抑制引起了类似的肾功能降低，但COX-2代谢物有助于而不是改善高血压。肾血流动力学的维持反映了Ang II和COX-2代谢物的直接和相反的作用。在水和电解质重吸收中的拮抗作用依赖于普遍的肾内Ang II活性。最近的功能实验表明，除了高血压、高血糖和氧化应激引起的炎症外，COX-2对Ang II有有益的调节作用。
Cyclooxygenase-2 (COX-2) plays a critical role in modulating deleterious actions of angiotensin II (Ang II) where there is an inappropriate activation of the renin-angiotensin system (RAS). This review discusses recent developments regarding the complex interactions by which COX-2 modulates the impact of an activated RAS on kidney function and blood pressure. Normal rats with increased COX-2 activity but with different intrarenal Ang II activity due to sodium restriction or chronic treatment with angiotensin converting enzyme (ACE) inhibitors showed similar responses to COX-2 selective inhibition (nimesulide) indicating independence from the intrarenal Ang II activity. COX-2 dependent maintenance of medullary blood flow was consistent and not dependent on dietary salt or ACE inhibition. In contrast, COX-2 influences on sodium excretion were contingent on the prevailing RAS activity. In chronic hypertensive models, COX-2 inhibition elicited similar reductions in kidney function but COX-2 metabolites contribute to rather than ameliorate the hypertension. The maintenance of renal hemodynamics reflects direct and opposing effects of Ang II and COX-2 metabolites. The antagonism in water and electrolyte reabsorption is dependent on the prevailing intrarenal Ang II activity. The recent functional experiments demonstrate a beneficial modulation of Ang II by COX-2 except in the presence of inflammation promoted by hypertension, hyperglycemia and oxidative stress.