Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan, Hubei 430030, China.
Chin Med J (Engl). 2013;126(17):3251-8.
Obstructive sleep apnea (OSA) has been recognized as an independent risk factor for systemic hypertension. The study investigated the functional consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced by angiotensin II (Ang II) and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase (MLCK), myosin phosphatase targeting subunit (MYPT1) and myosin light chain (MLC).
Male Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles. Phosphorylation of ERK1/2, MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 (10 µmol/L).
CIH-exposure resulted in more body weight gain and elevated blood pressure, which could be attenuated by pretreatment with PD98059. Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang II (Emax: (138.56 ± 5.78)% versus (98.45±5.31)% of KCl; pD2: 7.98 ± 0.14 versus 8.14 ± 0.05, respectively). CIH procedure exerted complex effects on ERK expressions (total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2 increased). CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC. In parallel to greater increases in phosphorylation of ERK1/2, MYPT1 and MLC, Ang II-induced aortic constriction was significantly enhanced in CIH rats, which was largely reversed by PD98059. However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation.
These data suggest that CIH exposure results in aortic hyperresponsiveness to Ang II, presumably owing to more activated ERK1/2 signaling pathway.
阻塞性睡眠呼吸暂停（OSA）已被认为是全身高血压的独立危险因素。本研究探讨了慢性间歇性低氧（CIH）对血管紧张素 II（Ang II）诱导的主动脉收缩的功能后果，以及涉及 ERK1/2 和收缩蛋白（如肌球蛋白轻链激酶（MLCK）、肌球蛋白磷酸酶靶亚单位（MYPT1）和肌球蛋白轻链（MLC））的可能信号。
雄性 Wistar 大鼠随机分为 CIH 组和常氧组，并分别暴露于 CIH 程序或空气-空气循环中。在存在或不存在 PD98059（10µmol/L）的情况下，通过血管收缩研究评估 ERK1/2、MYPT1 和 MLC 的磷酸化。
CIH 暴露导致体重增加和血压升高，这些可被 PD98059 预处理所减轻。来自 CIH 大鼠的去内皮主动脉环对 Ang II 的收缩敏感性更高（Emax：（138.56±5.78）%对 KCl 的（98.45±5.31）%；pD2：7.98±0.14 对 8.14±0.05）。CIH 程序对 ERK 表达产生了复杂的影响（总 ERK1/2 减少，而磷酸化与总 ERK1/2 的比值增加）。CIH 主动脉的 MLCK mRNA 和基础状态下的 MYPT1 和 MLC 磷酸化水平较高。与 ERK1/2、MYPT1 和 MLC 磷酸化的更大增加相平行，Ang II 诱导的主动脉收缩在 CIH 大鼠中显著增强，这在很大程度上被 PD98059 逆转。然而，常氧大鼠的血管收缩保持不变，尽管蛋白磷酸化的变化趋势相似但较小。
这些数据表明，CIH 暴露导致主动脉对 Ang II 的反应性增强，可能归因于更活跃的 ERK1/2 信号通路。
