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 in the incidence of fatal myocardial infarction in women. However, the effects 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 Zealand White rabbits were suspended in organ baths containing Krebs' solution; isometric tension was measured. Tamoxifen (0.1-100 microM) 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 effect on calcium concentration-dependent contraction curves. These data suggest that tamoxifen has beneficial effects on coronary reactivity that could, at least in part, account for the reduction in risk of fatal myocardial infarction in women taking tamoxifen.
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Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Webb
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Collins
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D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D011960:Receptors, Estrogen / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D017609:Barium Compounds; D002121:Calcium Channel Blockers; D002712:Chlorides; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C024986:barium chloride; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D019331:NG-Nitroarginine Methyl Ester