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RESEARCH COMMUNICATION |
a Vascular Biology Research Centre, Biomedical Sciences Division, King's College London, London W8 7AH, U.K.
b Neuroscience Research Centre, Biomedical Sciences Division, King's College London, Strand, London WC2R 2LS, U.K.
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 17ß-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 17ß-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.—Ruehlmann, D. O., Steinert, J. R., Valverde, M. A., Jacob, R., Mann, G. E. Environmental estrogenic pollutants induce acute vascular relaxation by inhibiting L-type Ca2+ channels in smooth muscle cells. FASEB J. 12, 613–619 (1998)
Key Words: environmental pollutants • DDT • nonylphenol • octylphenol • estrogen • antiestrogen • ICI 182,870 • Ca2+ and K+ channels • vascular smooth muscle cells • coronary vascular tone • heart
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