Babaei Hossein, Azarmi Yadollah
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Steroids. 2008 Sep;73(8):844-50. doi: 10.1016/j.steroids.2008.04.001. Epub 2008 Apr 10.
Studies suggest that estrogen modulate vascular reactivity but at present its exact mechanism of action has yet to be clarified. The aim of this study was to evaluate the effect of 17beta-estradiol (E2) on calcium-dependent and -independent contractions induced in the human saphenous veins (HSVs). HSVs were obtained from patients undergoing coronary artery bypass graft surgery. The ability of E2 to modulate Ca(2+) entry was assessed by obtaining concentration-response curve to CaCl(2) in the absence or presence of E2. In other experiments intracellular Ca(2+) was depleted by repeated application of phenylephrine in the presence of cyclopiazonic acid (CPA). Then, at the plateau of PGF(2alpha) contraction, E2 or nifedipine (NIF) was added. Involvement of protein kinase C (PKC) in relaxant effect of E2 was evaluated by application of phorbol-12,13-dibutyrate (PDBu) in normal or Ca(2+)-free Krebs' solution. When the contraction was obtained, E2 or NIF was added. In Ca(2+)-free hyperpolarizing solution, pretreatment with E2, concentration dependently reduced contractions induced by cumulative addition of calcium chloride. Furthermore, E2 elicited relaxant effects on the PGF(2alpha)-induced contractions in Ca(2+)-free solution in the presence or absence of CPA. Both E2 and NIF produced significant relaxation in HSV rings contracted by direct activation of PKC in Krebs' solution. However, in Ca(2+)-free solution, NIF failed to induce relaxant effect but E2 kept its effect on the PDBu-induced contraction. These results suggest that the relaxant effect of E2 on HSV is elicited by calcium-dependent and -independent pathways. The calcium-independent pathway may involve PKC inhibition.
研究表明，雌激素可调节血管反应性，但目前其确切作用机制尚待阐明。本研究旨在评估17β-雌二醇（E2）对人隐静脉（HSV）中钙依赖性和非钙依赖性收缩的影响。HSV取自接受冠状动脉搭桥手术的患者。通过在有无E2的情况下获得对氯化钙的浓度-反应曲线，评估E2调节Ca(2+)内流的能力。在其他实验中，在环匹阿尼酸（CPA）存在的情况下，通过重复应用去氧肾上腺素耗尽细胞内Ca(2+)。然后，在PGF(2α)收缩的平台期，加入E2或硝苯地平（NIF）。通过在正常或无Ca(2+)的Krebs溶液中应用佛波醇-12,13-二丁酸酯（PDBu），评估蛋白激酶C（PKC）在E2舒张作用中的参与情况。当获得收缩时，加入E2或NIF。在无Ca(2+)的超极化溶液中，E2预处理浓度依赖性地降低了氯化钙累积添加诱导的收缩。此外，在有无CPA的情况下，E2在无Ca(2+)溶液中对PGF(2α)诱导的收缩产生舒张作用。在Krebs溶液中，E2和NIF都能使通过直接激活PKC而收缩的HSV环产生显著舒张。然而，在无Ca(2+)溶液中，NIF未能诱导舒张作用，但E2对PDBu诱导的收缩仍保持其作用。这些结果表明，E2对HSV的舒张作用是通过钙依赖性和非钙依赖性途径引发的。非钙依赖性途径可能涉及PKC抑制。
