慢性间歇性缺氧(CIH)可导致血管功能紊乱,增加心血管疾病的发生风险。脑血管疾病,和动脉疾病。然而,CIH诱导血管功能障碍的机制尚不清楚.在这里,这项研究分析了主动脉平滑肌钙激活钾(BK)通道在CIH诱导的血管功能障碍中的作用。在大鼠和大鼠主动脉平滑肌细胞(RASMC)中建立CIH模型。血流动力学参数,如平均血压(MBP),舒张压(DBP),测量大鼠的收缩压(SBP),以及血管张力的评估。检测大鼠血清中NO和ET-1水平,ET-1,NO,eNOS,p-eNOS,氧化应激标志物(ROS和MDA),在主动脉组织中检测炎症因子(IL-6和TNF-α)。研究了RASMC中的Ca2+浓度。在主动脉组织和RASMC中评估了BK通道(BKα和BKβ)的活性。SBP,DBP,在CIH处理的大鼠中MBP升高,随着内皮功能障碍,细胞水肿和内皮细胞部分脱离。在CIH处理的大鼠和RASMC中,BK通道活性降低。BK通道激活增加eNOS,p-eNOS,和NO水平,同时降低ET-1,ROS,MDA,CIH处理大鼠的IL-6和TNF-α水平。CIH建模后,RASMC中的Ca2浓度增加,被BK通道激活逆转。BK通道抑制剂(伊贝毒素)exerbatedCIH诱导的血管疾病和内皮功能障碍。BK通道激活促进血管舒张,同时抑制血管内皮功能障碍,炎症,和氧化应激,从而间接改善CIH诱导的血管功能障碍。
Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.