title: Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin-angiotensin system in experimental arthritis.
abstract: 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.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 11361-87 Avenue, Edmonton, AB, T6G 2E1, Canada.
authors.forename: Waheed
authors.initials: W
authors.lastname: Asghar
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 11361-87 Avenue, Edmonton, AB, T6G 2E1, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Aghazadeh-Habashi
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 11361-87 Avenue, Edmonton, AB, T6G 2E1, Canada. fjamali@ualberta.ca.
authors.forename: Fakhreddin
authors.initials: F
authors.lastname: Jamali
keywords: AT2); Adjuvant arthritis; Angiotensin 1-7 (Ang1-7); Angiotensin II (AngII); Angiotensin converting enzyme (ACE); Angiotensin receptor (AT1; Cardiotoxicity; Chymase; MAS; NEP; NSAIDs; Renin angiotensin system (RAS)