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Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin–angiotensin system in experimental arthritis

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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.

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Acknowledgements

This work was supported in part by a Canadian Institute of Health Research and a Self-funded University of Alberta Research grant. WA was a recipient of an Islamia University of Bahawalpur scholarship.

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Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 11361-87 Avenue, Edmonton, AB, T6G 2E1, Canada

    Waheed Asghar, Ali Aghazadeh-Habashi & Fakhreddin Jamali

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  1. Waheed Asghar
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  2. Ali Aghazadeh-Habashi
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  3. Fakhreddin Jamali
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AAH and WA had equal contribution in designing and conduction of the experiments, collection and analysis of the results and drafting of the manuscript.

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Correspondence to Fakhreddin Jamali.

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Asghar, W., Aghazadeh-Habashi, A. & Jamali, F. Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin–angiotensin system in experimental arthritis. Inflammopharmacol 25, 543–553 (2017). https://doi.org/10.1007/s10787-017-0344-1

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