Department of Pharmacology, Xi'an Jiaotong University, College of Medicine, Xi'an, China.
Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H2097-106. doi: 10.1152/ajpheart.00701.2010. Epub 2010 Oct 8.
Myocardial infarction (MI) has been shown to induce endothelial dysfunction in peripheral resistance arteries and thus increase peripheral resistance. This study was designed to investigate the underlying mechanisms of post-MI-related dysfunctional dilatation of peripheral resistance arteries and, furthermore, to examine whether exercise may restore dysfunctional dilatation of peripheral resistance arteries. Adult male Sprague-Dawley rats were divided into three groups: sham-operated, MI, and MI + exercise. Ultrastructure and relaxation function of the mesenteric arteries, as well as phosphatidylinositol-3 kinase (PI3K), Akt kinases (Akt), endothelial nitric oxide synthase (eNOS) activity, and phosphorylation of PI3K, Akt, and eNOS by ACh were determined. Post-MI rats exhibited pronounced ultrastructural changes in mesenteric artery endothelial cells and endothelial dysfunction. In addition, the activities of PI3K, Akt, and eNOS, and their phosphorylation by ACh were significantly attenuated in mesenteric arteries (P < 0.05-0.01). After 8 wk of exercise, not only did endothelial cells appeared more normal in structure, but also ameliorated post-MI-associated mesenteric arterial dysfunction, which were accompanied by elevated activities of PI3K, Akt, and eNOS, and their phosphorylation by ACh (P < 0.05-0.01). Importantly, inhibition of either PI3K or eNOS attenuated exercise-induced restoration of the dilatation function and blocked PI3K, Akt, and eNOS phosphorylation by ACh in the mesenteric arteries. These data demonstrate that MI induces dysfunctional dilation of peripheral resistance arteries by degradation of endothelial structural integrity and attenuating PI3K-Akt-eNOS signaling. Exercise may restore dilatation function of peripheral resistance arteries by protecting endothelial structural integrity and increasing PI3K-Akt-eNOS signaling cascades.
心肌梗死（MI）已被证明可诱导外周阻力动脉的内皮功能障碍，从而增加外周阻力。本研究旨在探讨 MI 后相关的外周阻力动脉功能障碍性扩张的潜在机制，并进一步研究运动是否可以恢复外周阻力动脉的功能障碍性扩张。成年雄性 Sprague-Dawley 大鼠分为三组：假手术组、MI 组和 MI+运动组。检测肠系膜动脉的超微结构和舒张功能，以及磷脂酰肌醇-3 激酶（PI3K）、Akt 激酶（Akt）、内皮型一氧化氮合酶（eNOS）活性以及 ACh 对 PI3K、Akt 和 eNOS 的磷酸化。MI 大鼠表现出肠系膜动脉内皮细胞明显的超微结构变化和内皮功能障碍。此外，PI3K、Akt 和 eNOS 的活性及其 ACh 磷酸化明显减弱（P <0.05-0.01）。经过 8 周的运动后，不仅内皮细胞结构更加正常，而且改善了 MI 相关的肠系膜动脉功能障碍，同时还伴有 PI3K、Akt 和 eNOS 的活性及其 ACh 磷酸化增加（P <0.05-0.01）。重要的是，PI3K 或 eNOS 的抑制均可减弱运动引起的舒张功能恢复，并阻断肠系膜动脉中 ACh 对 PI3K、Akt 和 eNOS 的磷酸化。这些数据表明，MI 通过降解内皮结构完整性和减弱 PI3K-Akt-eNOS 信号通路引起外周阻力动脉的功能障碍性扩张。运动可能通过保护内皮结构完整性和增加 PI3K-Akt-eNOS 信号级联来恢复外周阻力动脉的舒张功能。
