Peixoto Pollyana, Aires Rosária Dias, Lemos Virgínia Soares, Bissoli Nazaré Souza, Santos Roger Lyrio Dos
Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Life Sci. 2017 Aug 15;183:21-27. doi: 10.1016/j.lfs.2017.06.020. Epub 2017 Jun 20.
The action of oestrogen has traditionally been attributed to the activation of nuclear receptors (ERα and ERβ). A third receptor, the G protein-coupled oestrogen receptor (GPER), has been described as mediator of the rapid action of oestrogen. Based on the possible protective role of oestrogen in the cardiovascular system, the present study was designed to determine whether selective GPER activation induces relaxation of mesenteric resistance arteries in both sexes and which signalling pathways are involved.
Third-order mesenteric arteries were isolated, and concentration-response curves were plotted following the cumulative addition of the selective GPER agonist G-1 (1nM-10μM) following induction of contraction with phenylephrine (3μM). The vasodilatory effects of G-1 were assessed before and after removal of the endothelium or incubation for 30min with nitric oxide synthase (N-nitro-L-arginine methyl ester - L-NAME, 300μM) and cyclooxygenase (indomethacin - INDO, 10μM) inhibitors alone or combined, PI3K-Akt pathway inhibitor (LY-294,002, 2.5μM) or a potassium channel blocker (tetraethylammonium - TEA, 5mM). GPER immunolocalisation was also performed on the investigated arteries.
The tested GPER agonist induced concentration-dependent relaxation of the mesenteric resistance arteries without differences related to sex that were partially endothelium dependent, mainly mediated by the PI3K-Akt-eNOS pathway and attenuated by nonspecific potassium channel blockade. In addition, the endothelial GPER immunolocalisation was stronger among females.
This evidence provides a new perspective for understanding the mechanisms involved in the vascular responses triggered by oestrogen via GPER in both sexes.
传统上认为雌激素的作用是通过激活核受体（ERα和ERβ）来实现的。第三种受体，即G蛋白偶联雌激素受体（GPER），已被描述为雌激素快速作用的介质。基于雌激素在心血管系统中可能的保护作用，本研究旨在确定选择性激活GPER是否能诱导两性肠系膜阻力动脉舒张，以及涉及哪些信号通路。
分离出三级肠系膜动脉，在用去氧肾上腺素（3μM）诱导收缩后，依次累积添加选择性GPER激动剂G-1（1nM - 10μM），绘制浓度-反应曲线。在去除内皮或单独或联合使用一氧化氮合酶抑制剂（N-硝基-L-精氨酸甲酯 - L-NAME，300μM）和环氧化酶抑制剂（吲哚美辛 - INDO，10μM）、PI3K-Akt通路抑制剂（LY-294,002，2.5μM）或钾通道阻滞剂（四乙铵 - TEA，5mM）孵育30分钟前后，评估G-1的血管舒张作用。还对所研究的动脉进行了GPER免疫定位。
所测试的GPER激动剂诱导肠系膜阻力动脉浓度依赖性舒张，两性之间无差异，部分依赖于内皮，主要由PI3K-Akt-eNOS通路介导，并被非特异性钾通道阻断减弱。此外，女性内皮GPER免疫定位更强。
这一证据为理解雌激素通过GPER在两性中引发血管反应的机制提供了新的视角。
