Raloxifene acutely relaxes rabbit coronary arteries in vitro by an estrogen receptor-dependent and nitric oxide-dependent mechanism.
BACKGROUND
Selective estrogen receptor modulators (SERMs) have been defined as compounds that display tissue specificity with regard to estrogenic effects. They appear to share the beneficial effects of estrogen on bone and lipids but are not associated with an increased risk of breast or uterine carcinoma. Estrogen relaxes coronary arteries and has long-term protective effects on the vascular system. The effect of SERMs on the coronary vasculature is unknown. We therefore investigated the effects of the SERM raloxifene on isolated rabbit coronary arteries.


RESULTS
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 then measured. Raloxifene induced coronary arterial relaxation in male and female coronary arteries by an endothelium-dependent and estrogen receptor-dependent mechanism involving nitric oxide. Raloxifene also had a direct calcium antagonistic effect on the coronary myocyte. Estrogen, however, induced only endothelium-independent coronary arterial relaxation. The endothelium-dependent component of relaxation induced by raloxifene 10(-6) mol/L resulted in almost 100% (79+/-7% versus 43+/-3%, P<0.001) more relaxation than that induced by estrogen 10(-6) mol/L.


CONCLUSIONS
These data demonstrate that raloxifene has vascular relaxing properties. The surprising finding is that the receptor-dependent effects via the endothelium are observed in coronary arteries from both male and female animals.
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Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
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Webb
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Collins
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D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester