Mercury induces nuclear estrogen receptors to act as vasoconstrictors promoting endothelial denudation via the PI3K/Akt signaling pathway.

ABSTRACT

Cardiovascular diseases (CVD) are more frequent among postmenopausal women due to the decline of estrogen concentration in plasma. However, the role of the vascular modulator effect of estrogen is controversial, since it occurs both in physiological and pathological conditions, increasing or reducing vascular reactivity. As mercury is widely associated with the development of CVD, we investigated putative hazardous effects on the mechanisms that modulate vascular reactivity in aortic rings of female Wistar rats promoted by acute mercury exposure. Mercury increased vascular reactivity and oxidative stress possibly due to NADPH oxidase participation, increased production of cyclooxygenase-2 (COX-2) and thromboxane A2 (TXA2) formation. The metal also induced endothelial denudation in the aorta by reducing the bioavailability of nitric oxide (NO) and enhancing the activity of the PI3K/Akt signaling pathway. Mercury exposure also induced nuclear estrogen receptors (ERα, ERß) to act as vasoconstrictors. Our findings suggest that mercury might increase the chances of developing cardiovascular diseases in females and should be considered an important environmental risk factor.