Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells

2013 
Abstract Although chronic arsenic exposure is a well-known risk for cardiovascular disease and has a strong correlation with hypertension, the molecular pathogenesis underlying arsenic exposure-induced hypertension remains poorly understood. To delineate the pathogenesis, we examined changes in the mRNA levels of 2 angiotensin II Type I receptor (AT 1 R) subtypes, AT 1A R and AT 1B R, in a mouse aortic endothelial cell line, END-D. Quantitative real-time PCR analysis revealed significant increases in the mRNA levels of 2 AT 1 R subtypes, AT 1A R and AT 1B R following sodium arsenite (SA) treatment. Flow cytometry analysis revealed that SA increases the generation of reactive oxygen species (ROS) in a dose-dependent manner. In addition, western blot analysis revealed that SA enhances the phosphorylations of c-Jun N-terminal kinases (JNK) and activated protein 1 (AP-1). These phosphorylations were inhibited by N -acetylcysteine (NAC), an anti-oxidant. Finally, SA-induced AT 1 R expression was found to be prevented both by NAC and specific JNK inhibitor, SP6001325, strongly indicating that AT 1 R upregulation is a result of the ROS-mediated activation of the JNK signaling pathway. Taken together, our results indicate that arsenic indeed upregulates the AT 1 R expression, thus highlighting a role of arsenic-induced aberrant AT 1 R signaling in the pathogenesis of hypertension.
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