Bisphenol A exposure and myocardial ischemia and mitigation by L-arginine supplementation

Among adults without a history of cardiovascular diseases (CVD), we estimated the effects of urinary bisphenol A (BPA) and plasma nitric oxide metabolites (NO x ) on risks of 24-h ST-segment depression events (STDE) and T-wave inversion events (TIE), two indicators of myocardial ischemia, recorded in five types of leads (i.e., anterior, anterolateral, lateral, inferior and all leads) by 12-lead Holter monitors. Target genes for BPA exposure and myocardial ischemia were identified by network toxicology analyses. Furthermore, we explored whether L-arginine (L-Arg, a substrate for NO synthesis) supplementation (9 g/day) could mitigate the potential adverse effects of BPA exposure on STDE and TIE. Among the 105 participants included in the final analyses, urinary BPA concentrations were associated with significant increases in the numbers of 24-h STDE in anterior, anterolateral and all leads, and in the numbers of 24-h TIE in all five types of leads. The inverse associations between NO x and the numbers of 24-h STDE and TIE were weakened along with the increasing BPA concentrations. A total of 1287 potential target genes were found to be associated with the influence of BPA on myocardial ischemia. Biological processes such as "response to nitric oxide" and pathways such as "vascular smooth muscle contraction" were significantly enriched. L-Arg supplementation significantly attenuated the BPA-STDE and BPA-TIE associations in most types of leads. This cross-sectional analysis, conducted in adults without a history of CVD, revealed that exposure to BPA is associated with increases in indicators of myocardial ischemia. Moreover, the adverse cardiac effects of BPA can be effectively mitigated by supplementation with L-Arg. • BPA was associated with increased ST-segment depression and T-wave inversion events. • BPA weakened the protective effects of NO x against the risks of myocardial ischemia. • L-Arg supplementation mitigated the adverse myocardial effects of BPA.