Effects of angiotensin II receptor blockers on serum levels of epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids in patients admitted to a cardiovascular center

Abstract

Abstract Purpose Several clinical studies have demonstrated that angiotensin-converting enzyme inhibitors, but not angiotensin II receptor blockers (ARBs), reduce the risk of non-fatal myocardial infarction and cardiovascular mortality. We found that ARBs inhibited the activity of various cytochrome enzymes in arachidonic acid metabolism, resulting in decreased in vitro production of epoxyeicosatrienoic acids (EETs), which exhibit vasodilation and anti-inflammatory effects, and their subsequent metabolites, dihydroxyeicosatrienoic acids (DHETs). The present study examined the effects of ARBs on serum levels of EETs and DHETs in patients admitted to a cardiovascular center. Methods A total of 223 patients were enrolled, of which 107 were exposed to ARBs in this study. ARB-free individuals were defined as the control group (n = 116). Serum levels of EETs and DHETs were measured by liquid chromatography–tandem mass spectrometry. Multiple linear regression analyses were carried out to identify covariates for total serum levels of EETs and DHETs. Results A significant negative association was observed between ARB use and serum EET and DHET levels (p = 0.034), whereas a significant positive association was observed between the estimated glomerular filtration rate (eGFR) and serum EET and DHET levels (p = 0.007). The median serum total EET and DHET level in the ARB group tended to become lower than that in the control group, although the difference was not significant. Conclusion ARB use and eGFR were significantly associated with total serum levels of EETs and DHETs. Our results suggest that ARBs could affect the concentration of EETs in vivo.