Asghar Waheed, Aghazadeh-Habashi Ali, Jamali Fakhreddin
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 11361-87 Avenue, Edmonton, AB, T6G 2E1, Canada.
Inflammopharmacology. 2017 Apr 7. doi: 10.1007/s10787-017-0344-1.
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.
炎症性疾病的一种合并症是心血管和肾脏风险增加。此外，用于治疗疼痛和炎症的非甾体抗炎药（NSAIDs）也与此类风险增加有关。我们推测，炎症和NSAIDs通过激活肾素-血管紧张素系统（RAS）来增加心血管和肾脏风险，RAS是调节肾脏和心血管稳态的一条途径。我们研究了佐剂性关节炎和NSAIDs对RAS的影响。采用蛋白质免疫印迹法和酶联免疫吸附测定法来检测RAS的组分。炎症导致心脏和肾脏中的血管紧张素转换酶、其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（1型和2型AngII以及Ang1-7受体Mas）出现显著失衡，从而导致心血管和肾脏毒性。然而，用NSAIDs（罗非昔布、美洛昔康、塞来昔布和氟比洛芬）对患有关节炎的动物进行7天治疗可恢复其组成平衡，这可能归因于它们的抗炎特性。炎症通过导致RAS失衡发挥其对心血管和肾脏的影响。NSAIDs通过其抗炎作用恢复这种失衡。因此，NSAIDs心脏毒性可能涉及RAS失衡以外的机制。
