Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis

摘要: Nonsteroidal antiinflammatory drugs, including ibuprofen, are among the most commonly used medications and produce their effects by blocking cyclooxygenase (COX)-2. Their use is associated with increased risk of heart attacks caused COX-2 in vasculature and/or kidney, our recent work implicating endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), a cardiotoxic hormone whose can be prevented l-arginine. The ibuprofen salt arginate (Spididol) was created to increase solubility but we suggest that it could also augment NO pathway through codelivery arginine. Here investigated idea act simultaneously inhibit preserve pathway. Ibuprofen functioned similarly sodium for inhibition mouse/human COX-2, only served as substrate NOS. not reversed inhibitory ADMA NG-nitro-l-arginine methyl ester on inducible (macrophages) endothelial vitro (aorta) vivo (blood pressure). These observations show provides, one preparation, negate harmful cardiovascular consequences mediated renal ADMA. While remarkably simple, findings potentially game-changing nonsteroidal drug arena.-Kirkby, N. S., Tesfai, A., Ahmetaj-Shala, B., Gashaw, H. H., Sampaio, W., Etelvino, G., Leao, M., Santos, R. Mitchell, J. A. retains eNOS activity reverses dysfunction: implications COX-2/ADMA axis.