植物源性雌激素在体外通过钙拮抗机制使冠状动脉舒张。

Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism.

作者信息

Figtree G A, Griffiths H, Lu Y Q, Webb C M, MacLeod K, Collins P

机构信息

Cardiac Medicine, Imperial College School of Medicine, National Heart & Lung Institute, London, United Kingdom.

出版信息

J Am Coll Cardiol. 2000 Jun;35(7):1977-85. doi: 10.1016/s0735-1097(00)00645-8.

DOI:10.1016/s0735-1097(00)00645-8

PMID:10841251

Abstract

OBJECTIVES

To investigate the potential for plant derived estrogens (phytoestrogens) genistein, phloretin, biochanin A and zearalanone to relax rabbit coronary arteries in vitro and to determine the mechanism(s) of such relaxation.

BACKGROUND

Epidemiological data suggests a reduction in the incidence of coronary heart disease in humans who have a high intake of phytoestrogens.

METHODS

Isolated rabbit coronary artery rings were suspended in individual organ baths, precontracted with potassium chloride (30 mM), and the relaxing effects and mechanisms of relaxation to genistein, phloretin, biochanin A and zearalanone were determined by measurement of isometric tension.

RESULTS

Genistein, phloretin and biochanin A induced significant gender-independent relaxation in rings with and without endothelium. Inhibition of nitric oxide and prostaglandin synthesis with L-NAME and indomethacin had no effect on genistein-induced relaxation. Relaxation was unaffected by the specific estrogen receptor antagonist ICI 182,780, the ATP-sensitive potassium channel inhibitor glibenclamide and the potassium channel inhibitor, barium chloride. Calcium concentration-dependent contraction curves in high potassium depolarization medium were significantly shifted to the right and downward after incubation with genistein and zearalanone. An inhibitory effect of genistein (2 microM) on L-type calcium current in guinea-pig ventricular myocytes confirmed a calcium antagonist relaxing mechanism of action. In healthy volunteers, plasma genistein levels of approximately 2 microM are achieved after ingestion of a commercially available soy protein drink (Supro) containing 37 mg genistein.

CONCLUSIONS

This study demonstrates that phytoestrogens induce endothelium-independent relaxation of coronary arteries; the mechanism involves calcium antagonism. These mechanisms may contribute to the potential long-term cardiovascular protective effect of these substances.

摘要

目的

研究植物源性雌激素（植物雌激素）染料木黄酮、根皮素、鹰嘴豆芽素A和玉米赤霉烯酮在体外使兔冠状动脉舒张的可能性，并确定这种舒张的机制。

背景

流行病学数据表明，高摄入植物雌激素的人群中冠心病发病率降低。

方法

将分离的兔冠状动脉环悬挂于单个器官浴槽中，用氯化钾（30 mM）预收缩，通过测量等长张力来确定染料木黄酮、根皮素、鹰嘴豆芽素A和玉米赤霉烯酮的舒张作用及舒张机制。

结果

染料木黄酮, 根皮素和鹰嘴豆芽素A在有内皮和无内皮的冠状动脉环中均能引起显著的、不依赖性别的舒张。用L-NAME和吲哚美辛抑制一氧化氮和前列腺素合成对染料木黄酮诱导的舒张无影响。舒张不受特异性雌激素受体拮抗剂ICI 182,780、ATP敏感性钾通道抑制剂格列本脲和钾通道抑制剂氯化钡的影响。在高钾去极化培养基中，与染料木黄酮和玉米赤霉烯酮孵育后，钙浓度依赖性收缩曲线显著向右下方移动。染料木黄酮（2 microM）对豚鼠心室肌细胞L型钙电流的抑制作用证实了其钙拮抗剂的舒张作用机制。在健康志愿者中，摄入含有染料木黄酮37 mg的市售大豆蛋白饮料（Supro）后，血浆染料木黄酮水平可达到约2 microM。