Figtree G A, Lu Y, Webb C M, Collins P
Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Circulation. 1999 Sep 7;100(10):1095-101. doi: 10.1161/01.cir.100.10.1095.
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.
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.
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.
选择性雌激素受体调节剂（SERM）被定义为对雌激素作用具有组织特异性的化合物。它们似乎具有雌激素对骨骼和脂质的有益作用，但与乳腺癌或子宫癌风险增加无关。雌激素可舒张冠状动脉并对血管系统具有长期保护作用。SERM对冠状动脉血管系统的影响尚不清楚。因此，我们研究了SERM雷洛昔芬对离体兔冠状动脉的影响。
将成年雄性和未孕雌性新西兰白兔的冠状动脉环悬挂于含有 Krebs 溶液的器官浴槽中；然后测量等长张力。雷洛昔芬通过涉及一氧化氮的内皮依赖性和雌激素受体依赖性机制诱导雄性和雌性冠状动脉舒张。雷洛昔芬对冠状动脉心肌细胞也有直接的钙拮抗作用。然而，雌激素仅诱导非内皮依赖性冠状动脉舒张。10⁻⁶ mol/L 雷洛昔芬诱导的舒张的内皮依赖性成分导致的舒张比 10⁻⁶ mol/L 雌激素诱导的舒张多近 100%（79±7% 对 43±3%，P<0.001）。
这些数据表明雷洛昔芬具有血管舒张特性。令人惊讶的发现是，在雄性和雌性动物的冠状动脉中均观察到通过内皮的受体依赖性效应。
