Nonsteroidal anti-inflammatory drugs: Is there a link between cardiovascular and renal adverse effects?

"Both the clinical benefits and the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are mediated by the inhibition of cyclooxygenase (COX) 1 and 2.[1] COX-1 is expressed constitutively in tissues, whereas COX-2 is produced under periods of stress and inflammation. The physiologic function of COX-1 and COX-2 is to convert arachidonic acid to prostaglandins, thromboxane A2 (TXA2), and prostacyclins. These products influence multiple systems such as cardiac, immune, gastrointestinal (GI), renal, vascular, and pulmonary systems.[12] COX enzymes are present in various locations throughout the body including the blood vessels where they produce vasodilatory prostacyclins and TXA2, which causes platelet aggregation.[3] They are also present in the kidney where they help maintain renal blood flow and promote natriuresis, diuresis, and vasodilation through the production of prostaglandins. Inhibition of COX with the use of NSAIDs produces the well-known pain-relieving effects through decreased production of prostaglandins, which under physiologic conditions cause hyperalgesia.[14] Although NSAIDs remain guideline recommended for arthritis and musculoskeletal conditions, the use of NSAIDs does not come without risk of side effects. Well-known adverse effects of NSAIDs include GI bleeding, as well as cardiovascular and renal function changes.[24]"