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

Abstract

Tamoxifen is a mixed estrogen antagonist and agonist. Observational data from breast cancer studies associate tamoxifen use with lesser rates of myocardial infarction. The authors sought to determine the acute vasoactive properties of tamoxifen compared with estradiol. Isolated coronary ring segments from female pigs were studied in organ baths. KCl-precontracted ring segments were exposed to increasing doses of both tamoxifen and estradiol (log-9-log-5 M ). Ring segments were also exposed to tamoxifen and estradiol in the presence of inhibitors of nitric oxide, glybenclamide, the hormone receptor antagonists ICI 182,780 and flutamide, and after de-endothelialization. Tamoxifen caused acute dilation of coronary arteries but less than estradiol. Tamoxifen-and estradiol-induced acute vasodilation was not nitric oxide- or endothelium-dependent, but was adenosine triphosphate-sensitive potassium channel-dependent. Tamoxifen-induced vasorelaxation was inhibited by antagonism of the classic estrogen receptor and antagonism of the androgen receptor with flutamide, whereas estrogen-induced vasorelaxation was inhibited partially by classic estrogen receptor antagonism but not by androgen receptor antagonism. Tamoxifen attenuated both the sensitivity of vasoconstriction to endothelin-1 and the maximal response. Tamoxifen and estradiol are both acute coronary vasodilators, with similar mechanisms of action. Tamoxifen also attenuates coronary vasoconstriction. Such properties may account for some of the observed cardiovascular clinical benefits seen in observational studies of tamoxifen use.