Jodati Ahmad Reza, Babaei Hossein, Azarmi Yadollah, Fallah Sahar, Gharebageri Afsaneh, Fouladi Danial Fadaei, Safaei Naser
Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2015 Mar;5(1):89-96. doi: 10.5681/apb.2015.012. Epub 2015 Mar 5.
A protective effect for estrogens against cardiovascular problems has long been known. The aim of this study was to investigate the vasorelaxant effect of 17α-Ethynylestradiol (17α-EE) on human saphenous vein.
The veins were suspended horizontally between two triangular stainless steel hooks for the measurement of isometric tension in individual organ baths containing 10ml Krebs solution, at 37°C and gassed with carbogen under 3gr optimum tension. The effect of different concentrations of 17α-EE (2-40 μM) on vascular tone was investigated in veins precontracted with PGF2α. Relaxation was measured after 40min and expressed as the percent decrease of initial contraction. To determine the involvement of potassium channels, endothelium, nitric oxide synthase, guanylylcyclase and prostaglandins in the vasorelaxant effect of estrogen, the veins were incubated with tetraethyl ammonium, N-nitro-L-arginine methyl ester, methylene blue or indomethacin, respectively for 20min prior to experimentation. Responses to 17α-EE were directly compared to those obtained in the same tissues in the absence of the inhibitors.
The mean relaxations induced by 17α-EE with concentrations of 2, 5, 10, 20 and 40μM in tissues precontracted with PGF2α were 19.8 ±5.5%, 26.1±10.8%, 32.2±7.4%, 48.6±10.8%and56±7.6%, respectively. The results of the inhibition of potassium channels, nitric oxide synthase, guanylylcyclase, cyclooxygenase and removing endothelium in relaxation induced by 17α-EE on precontracted veins with PGF2α proved no significant differences.
This study showed that 17α-EE has significant vasorelaxant effect on human saphenous vein in a concentration-dependent manner. This effect is probably independent of potassium channels, nitric oxide synthase, guanylylcyclase, prostaglandin synthesis and endothelium functions.
雌激素对心血管问题具有保护作用这一点早已为人所知。本研究的目的是探究17α-乙炔雌二醇(17α-EE)对人隐静脉的血管舒张作用。
将静脉水平悬挂在两个三角形不锈钢钩之间,用于在含有10ml Krebs溶液、温度为37°C且用混合气充气、最佳张力为3克的单个器官浴中测量等长张力。在预先用前列腺素F2α预收缩的静脉中研究不同浓度的17α-EE(2 - 40μM)对血管张力的影响。40分钟后测量舒张情况,并表示为初始收缩减少的百分比。为了确定钾通道、内皮、一氧化氮合酶、鸟苷酸环化酶和前列腺素在雌激素血管舒张作用中的参与情况,在实验前分别将静脉与四乙铵、N-硝基-L-精氨酸甲酯、亚甲蓝或吲哚美辛孵育20分钟。将对17α-EE的反应与在不存在抑制剂的相同组织中获得的反应直接进行比较。
在预先用前列腺素F2α预收缩的组织中,浓度为2、5、10、20和40μM的17α-EE诱导的平均舒张分别为19.8±5.5%、26.1±10.8%、32.2±7.4%、48.6±10.8%和56±7.6%。在预先用前列腺素F2α预收缩的静脉中,17α-EE诱导的舒张中,抑制钾通道、一氧化氮合酶、鸟苷酸环化酶、环氧化酶和去除内皮的结果证明没有显著差异。
本研究表明,17α-EE对人隐静脉具有显著的血管舒张作用,且呈浓度依赖性。这种作用可能独立于钾通道、一氧化氮合酶、鸟苷酸环化酶、前列腺素合成和内皮功能。