Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin-angiotensin system in experimental arthritis
Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin-angiotensin system in experimental arthritis
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DOI：
10.1007/s10787-017-0344-1
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发表时间：
2017-10-01
影响因子：
5.8
通讯作者：
Jamali, Fakhreddin
中科院分区：
文献类型：
--
作者：
Asghar, Waheed;Aghazadeh-Habashi, Ali;Jamali, Fakhreddin
炎症的合并症是心肾风险的增加。此外，用于治疗疼痛和炎症的非甾体抗炎药（NSAIDs）也与此类风险的增加有关。我们假设炎症和非甾体抗炎药通过激活肾素-血管紧张素系统（RAS）来施加心肾风险，RAS是肾脏和心血管稳态的调节途径。我们研究了佐剂性关节炎和非甾体抗炎药对RAS的影响。采用免疫印迹法和酶联免疫吸附法测定RAS成分。炎症导致心脏和肾脏血管紧张素转换酶、它们的生物活性血管紧张素肽（AngII和Ang1-7）以及参与肽受体结合的靶蛋白（AngII 1型和2型以及Ang1-7受体，Mas）的显著失衡，从而导致心肾毒性。然而，用非甾体抗炎药（罗非昔布、美洛昔康、塞来昔布和氟比洛芬）治疗关节炎动物7天后，可能是由于它们的抗炎特性，恢复了组成平衡。炎症通过引起RAS失衡来发挥其心肾作用。非甾体抗炎药通过其抗炎作用恢复这种不平衡。因此，非甾体抗炎药的心脏毒性可能与RAS失衡以外的机制有关。
A co-morbidity of inflammatory conditions is increased cardio-renal risks. Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) which are used to treat pain and inflammation are also associated with increase in such risks. We hypothesized that inflammation and NSAIDs impose the cardio-renal risk through the activation of the renin-angiotensin-system (RAS), a regulating pathway of the renal and cardiovascular homeostasis. We investigated the effect of adjuvant arthritis and NSAIDs on the RAS. Western blotting and ELISA were used to measure the RAS components. Inflammation caused significant imbalances in the cardiac and renal angiotensin converting enzymes, their biologically active angiotensin peptides (AngII and Ang1-7) and the target proteins involved in the peptide-receptor binding (AngII type 1 and type 2, and Ang1-7 receptor, Mas) toward cardio-renal toxicity. However, 7 days treatment of arthritic animals with NSAIDs (rofecoxib, meloxicam, celecoxib and flurbiprofen) restored the constitutive balances, perhaps due to their anti-inflammatory properties. Inflammation exerts its cardio-renal effects by causing imbalance in the RAS. NSAIDs through their anti-inflammatory effect restore this imbalance. Thus, mechanisms other than imbalances in the RAS may be involved in the NSAIDs cardiotoxicity.