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.
Ruehlmann
D O
DO
Vascular Biology Research Centre, Biomedical Sciences Division, King's College London, UK.
Steinert
J R
JR
Valverde
M A
MA
Jacob
R
R
Mann
G E
GE
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004785:Environmental Pollutants / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007306:Insecticides / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004785:Environmental Pollutants; D004965:Estrogen Antagonists; D004967:Estrogens; D007306:Insecticides; D010636:Phenols; D015221:Potassium Channels; D000077267:Fulvestrant; D004958:Estradiol; C080417:4-octylphenol; C041594:4-nonylphenol