Tamoxifen is an acute, estrogen-like, coronary vasodilator of porcine coronary arteries in vitro

Tamoxifen is a mixed estrogen antagonist and agonist. Observational data fr om breast cancer studies associate tamoxifen use with lesser rates of myoca rdial infarction. The authors sought to deter-mine the acute vasoactive pro perties of tamoxifen compared with estradiol. Isolated coronary ring segmen ts from female pigs were studied in organ baths. KCI-precontracted ring seg ments were exposed to increasing doses of both tamoxifen and estradiol (log -9-log-5M). Ring segments were also exposed to tamoxifen and estradiol in t he presence of inhibitors of nitric oxide, glybenclamide, the hormone recep tor antagonists ICI 182,780 and flutamide, and after de-endothelialization. Tamoxifen caused acute dilation of coronary arteries but less than estradi ol. Tamoxifen- and estradiol-induced acute vasodilation was not nitric oxid e- or endothelium-dependent, but was adenosine triphosphate-sensitive potas sium channel-dependent. Tamoxifen-induced vasorelaxation was inhibited by a ntagonism of the classic estrogen receptor and antagonism of the androgen r eceptor with flutamide, whereas estrogen-induced vasorelaxation was inhibit ed partially by classic estrogen receptor antagonism but not by androgen re ceptor antagonism. Tamoxifen attenuated both the sensitivity of vasoconstri ction to endothlin-1 and the maximal response. Tamoxifen and estradiol are both acute coronary vasodilators, with similar mechanisms of action. Tamoxi fen also attenuates coronary vasoconstriction. Such properties may account for some of the observed cardiovascular clinical benefits seen in observati onal studies of tamoxifen use.