Environmental estrogenic pollutants induce acute vascular relaxation by inhibiting L-type Ca2+ channels in smooth muscle cells

There is an ongoing scientific debate concerning the potential threat of environmental estrogenic pollutants to animal and human health (1-5). Pollutants including the detergents 4-octylphenol and p-nonylphenol and chlorinated insecticides have recently been reported to modulate sexual differentiation by interacting with nuclear steroid receptors (6-8). So far, the focus has been on reproductive organs, but sex steroids have far more widespread actions. The lower incidence of cardiovascular disease in women has been attributed to estrogens (9-14), yet no information is available on the vascular actions of environmental estrogenic pollutants. In the present study we have investigated the effects of acute exposure to 17beta-estradiol, the antiestrogen ICI 182,780, and estrogenic pollutants on coronary vascular tone as well as on intracellular Ca2+ levels ([Ca2+]i) and Ca2+ and K+ channel activity in vascular smooth muscle cells. We report here that 4-octylphenol, p-nonylphenol, o.p'-DDT, and the antiestrogen ICI 182,780 inhibit L-type Ca2+ channels in vascular smooth muscle cells and evoke a rapid and endothelium-independent relaxation of the coronary vasculature similar to that induced by 17beta-estradiol. Thus, inhibition of Ca2+ influx via L-type Ca2+ channels in vascular smooth muscle cells may explain the acute, nongenomic vasodilator actions of environmental estrogenic pollutants.