Tamoxifen acutely relaxes coronary arteries by an endothelium-, nitric oxide-, and estrogen receptor-dependent mechanism

In epidemiological studies tamoxifen has been associated with a reduction i n the incidence of fatal myocardial infarction in women. However, the effec ts of tamoxifen on coronary artery reactivity are unknown. We hypothesized that tamoxifen would relax precontracted isolated rabbit coronary arteries. Rings of coronary artery from adult male and nonpregnant female New Zealan d White rabbits were suspended in organ baths containing Krebs' solution; i sometric tension was measured. Tamoxifen (0.1-100 muM) induced significant endothelium-dependent relaxation in precontracted rabbit coronary arteries. This relaxation was inhibited by N-omega-nitro-L-arginine methyl ester and the estrogen receptor antagonist ICI 182,780. There was no significant eff ect on calcium concentration-dependent contraction curves. These data sugge st that tamoxifen has beneficial effects on coronary reactivity that could, at least in part, account for the reduction in risk of fatal myocardial in farction in women taking tamoxifen.