17-β-oestradiol-induced vasorelaxation in vitro is mediated by eNOS through hsp90 and akt/pkb dependent mechanism
17-β-oestradiol-induced vasorelaxation in vitro is mediated by eNOS through hsp90 and akt/pkb dependent mechanism
复制标题
DOI：
10.1038/sj.bjp.0704641
复制
发表时间：
2002-04-01
影响因子：
7.3
通讯作者：
Cirino, G
中科院分区：
文献类型：
--
作者：
Bucci, M;Roviezzo, F;Cirino, G
1 L-精氨酸-NO通路与17-β-雌二醇的血管舒张作用有关。在这里，我们已经解决了两个不同的激活步骤的内皮型一氧化氮合酶（eNOS）的参与17-β-雌二醇诱导的大鼠主动脉环的血管舒张作用。2大鼠主动脉环收缩与苯肾上腺素（PE）1 μ M放松浓度相关的方式，以17-β-octane水溶性环糊精包封（E2）只有当内皮细胞。E2受体10的纯抗雌激素182，780（20 μ M）显著抑制E2诱导的血管舒张。3格尔德霉素（10 μ m），热休克蛋白90（hsp 90）和N-无限-硝基-L-精氨酸甲酯的特异性抑制剂（L-NAME，100 μ M），一氧化氮合酶抑制剂，显著抑制E2诱导的血管舒张。4用LY 294002（25 μ M）孵育大鼠主动脉环长达6小时，PI（3）K akt/pkb途径的特异性抑制剂可减少E2诱导的血管舒张。5用E2孵育大鼠离体主动脉，诱导前列环素（PGI（2））释放。布洛芬（10 μ M）消除了PGI（2）水平（以6-酮PGF（1 α）测量），L-NAME和GA均不影响基础或E2刺激的PGI（2），证实了这两种化合物对eNOS通路的特异性。我们证明，E2与其受体相互作用后，通过HSP 90和Akt/Akt介导eNOS激活，在大鼠主动脉环中产生血管舒张作用。pkb依赖机制。
1 The L-arginine-NO pathway has been implicated in the vasorelaxant effect of 17-beta-oestradiol. Here we have addressed the involvement of two distinct activation steps of endothelial nitric oxide synthase (eNOS) in the 17-beta-oestradiol-induced vasorelaxant effect on rat aortic rings.2 Rat aortic rings contracted with phenylephrine (PE) 1 muM relaxed in a concentration related fashion to 17-beta-ocstradiol water soluble cyclodextrin-encapsulated (E2) only when endothelium was present. The pure anti-oestrogen of E2 receptor 10 182,780 (20 muM) significantly inhibited E2-induced vasorelaxation.3 Geldanamycin (10 pm), a specific inhibitor of heat shock protein 90 (hsp90) and N-infinity-nitro-L-arginine-methyl ester (L-NAME, 100 muM), a nitric oxide synthase inhibitor, significantly inhibited E2-induced vasorelaxation.4 Incubation of rat aortic rings up to 6 h with LY 294002 (25 muM), a specific inhibitor of PI(3)K akt/pkb pathway reduced E2-induced vasorelaxation.5 Incubation of rat isolated aorta with E2, induced prostacyclin (PGI(2)) release. PGI(2) levels, measured as 6-keto PGF(1alpha), were abolished by ibuprofen (10 muM), both L-NAME and GA did not influence basal or E2-stimulated PGI(2) confirming the specificity of these two compounds on eNOS pathway.6 In conclusion, we demonstrate that E2 interaction with its receptor is followed by a vasorelaxant effect in rat aortic rings mediated by eNOS activation through both hsp90 and akt/pkb dependent mechanisms.