Grant: Travel Awards - Institute Community Support

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of pain and inflammation caused by arthritis and such other rheumatic diseases. Arthritis is not only a disease of the elderly, but children can also be affected by the disease. According to WHO there are 1.2 billion arthritis patients around the world, 51 million in US and 4.2 million in Canada. About 30-50% of the arthritis patients are chronic user of NSAIDs, but their use is restricted due to their side effects of the various bodily systems including cardiovascular (CV) system through unknown mechanisms. Recently, we have reported that a major blood pressure controlling mechanism in the body called renin angioten system (RAS) and its metabolic product peptides (cardiotoxic-ANGII; cardioprotective-ANG1-7) are disrupted in the rat heart under inflammatory condition. Studies have shown that most of cardiovascular disease have an inflammatory component involved in their pathogenesis. Simultaneously, the use of NSAIDs for treatment of such inflammatory condition have also been reported to adversely influence the cardiac function. Thus, we aimed to assess if inflammation and NSAIDs can influence the RAS by altering the activity of ists enzymes (ACE and ACE2)and their active metabolic products (Ang-II, Ang1-7). We studied this in rat heart in a model of rheumatoid arthritis , using Enzyme-linked immunosorbent assay (ELISA). We concluded that both inflammation and NSAIDs influnece the RAS by altering its component enzymes (ACE, ACE2). This results in a results in a significant increase in their metabolic product peptides namely; cardiotoxic(Ang-II)and cardioprotective(Ang-1-7). But for those NSAIDs that are know for their cardiotoxic potential the proportional(i.e. rofecoxib) the increase in cardiotoxic peptide (Ang-II) is more compared to the increase in cardioprotective peptide (Ang01-7). That might explains the increased risk of cardiotoxicity associated with the use of some NSAIDs.