背景:雌激素对脉管系统的保护作用不能仅通过其通过受体ERα和ERβ的作用来解释。G蛋白偶联的雌激素受体(GPER)-广泛分布在整个心血管系统中-也可能参与该反应。然而,对GPER在高血压中的作用知之甚少。因此,在这项研究中,我们使用特定的激动剂评估了GPER介导的血管反应,自发性高血压大鼠(SHR)中的G-1。我们假设G-1会在两性SHR的阻力肠系膜动脉中引起放松反应。
方法:在两性SHR的肠系膜动脉中进行G-1浓度-反应曲线(1nM-10μM)(10-12周龄,重180-250克)。在去除内皮之前和之后,用单独的抑制剂L-NAME(300μM)和吲哚美辛(10μM)或与克霉唑(0.75μM)或过氧化氢酶(1,000单位/mL)组合孵育30分钟,评估G-1的作用。还研究了GPER免疫定位,使用二氯荧光素(DCF)和二氢乙锭(DHE)染色评估血管过氧化氢(H2O2)和ROS,分别。
结果:GPER激活在雌性和雄性高血压大鼠的阻力肠系膜动脉中促进了类似的松弛反应,但有不同内皮介质的参与。男性似乎更依赖于NO途径,其次是H2O2途径,和雌性在内皮和H2O2途径上。
结论:这些发现表明,GPER激动剂G-1可以以相似的方式在两种性别的高血压大鼠的肠系膜动脉中诱导舒张反应,尽管有内皮介质的不同参与。这些结果有助于理解GPER激活对原发性高血压患者肠系膜动脉阻力的影响。
BACKGROUND: The protective effect of estrogen on the vasculature cannot be explained only by its action through the receptors ERα and ERβ. G protein-coupled estrogen receptors (GPER)-which are widely distributed throughout the cardiovascular system-may also be involved in this response. However, little is known about GPER actions in hypertension. Therefore, in this study we evaluated the vascular response mediated by GPER using a specific agonist, G-1, in spontaneously hypertensive rats (SHR). We hypothesized that G-1 would induce a relaxing response in resistance mesenteric arteries from SHR of both sexes.
METHODS: G-1 concentration-response curves (1 nM-10 μM) were performed in mesenteric arteries from SHR of both sexes (10-12-weeks-old, weighing 180-250 g). The effects of G-1 were evaluated before and after endothelial removal and incubation for 30 min with the inhibitors L-NAME (300 μM) and indomethacin (10 μM) alone or combined with clotrimazole (0.75 μM) or catalase (1,000 units/mL). GPER immunolocalization was also investigated, and vascular hydrogen peroxide (H2O2) and ROS were evaluated using dichlorofluorescein (DCF) and dihydroethidium (DHE) staining, respectively.
RESULTS: GPER activation promoted a similar relaxing response in resistance mesenteric arteries of female and male hypertensive rats, but with the participation of different endothelial mediators. Males appear to be more dependent on the NO pathway, followed by the H2O2 pathway, and females on the endothelium and H2O2 pathway.
CONCLUSIONS: These findings show that the GPER agonist G-1 can induce a relaxing response in mesenteric arteries from hypertensive rats of both sexes in a similar way, albeit with differential participation of endothelial mediators. These results contribute to the understanding of GPER activation on resistance mesenteric arteries in essential hypertension.