Inorganic arsenic exposure induces sex-disparate effects and exacerbates ischemia-reperfusion injury in the female heart

作者：Ryne Veenema, Kevin M. Casin, Prithvi Sinha, Raihan Kabir, Nathan Mackowski, Nicole Taube, Djahida Bedja, Rui Chen, Ana M. Rule, Mark J. Kohr · 发表于：American Journal of Physiology-Heart and Circulatory Physiology · 年份：2019 · DOI：10.1152/ajpheart.00364.2018 · 被引用次数：25 · 研究领域：Heavy Metal Exposure and Toxicity、Arsenic contamination and mitigation、Electrochemical Analysis and Applications

Arsenic is a common contaminant in drinking water throughout the world, and recent studies support a link between inorganic arsenic (iAS) exposure and ischemic heart disease in men and women. Female hearts exhibit an estrogen-dependent reduction in susceptibility to myocardial ischemic injury compared with males, and as such, female hearts may be more susceptible to the endocrine-disrupting effects of iAS exposure. However, iAS exposure and susceptibility to ischemic heart injury have not been examined in mechanistic studies. Male and female mice (8 wk) were exposed to environmentally relevant concentrations of sodium arsenite (0, 10, 100, and 1,000 parts/billion) via drinking water for 4 wk. Pre- and postexposure echocardiography was performed, and postexposure plasma was collected for 17β-estradiol measurement. Hearts were excised and subjected to ischemia-reperfusion (I/R) injury via Langendorff perfusion. Exposure to 1,000 parts/billion iAS led to sex-disparate effects, such that I/R injury was exacerbated in female hearts but unexpectedly attenuated in males. Assessment of echocardiographic parameters revealed statistically significant structural remodeling in iAS-treated female hearts with no change in function; males showed no change. Plasma 17β-estradiol levels were not significantly altered by iAS in male or female mice versus nontreated controls. Although total eNOS protein levels did not change in whole heart homogenates from iAS-treated male or female mice, eNOS p...