Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite 500 (ICBS), 90050-170, Porto Alegre, Rio Grande do Sul, Brazil.
J Physiol Biochem. 2014 Jun;70(2):363-74. doi: 10.1007/s13105-013-0310-3. Epub 2014 Jan 7.
Previous studies from our laboratory have demonstrated that a single bout of moderate exercise stimulates macrophage function, increasing phagocytic capacity, and production of hydrogen peroxide and nitric oxide (NO˙) through nuclear factor kappa B activation. In this work, we investigated the role of α- and β-adrenoreceptors on the function of monocyte/macrophages during rest and exercise. Adult male Wistar rats were i.p. administered (100 μL/100 g) with specific adrenergic antagonists before an acute moderate exercise bout: prazosin (α1-specific antagonist 2 mg/kg), propranolol (unspecific β1/β2 antagonist 10 mg/kg), double blockade (α1 and β1/β2), or phosphate-buffered saline (control). Acute exercise consisted in a single swimming session of moderate intensity (5% body weight overload on the chest) for 60 min. Control groups (rest) received the same antagonists and were killed 60 min after drug administration. Exercise increased phagocytic capacity (1.7-fold, p < 0.05), NO˙ production (5.24 fold, p < 0.001), and inducible nitric oxide synthase (NOS2) expression (by 58.1%), thus suggesting macrophage activation. The β-adrenoreceptor blockade did not change this behavior. In resting animals, α1 antagonist, as well as the double (α1/β) blockade, however, further increased phagocytic capacity (by up to 261%, p < 0.001), NO˙ production (by up to 328%, p < 0.001), and the expressions of NOS2 (by 182%, p < 0.001) and HSP70 (by 42.5%, p < 0.01) suggesting a tonic inhibitory effect of α1 stimulation on macrophage activation. In exercised animals, α1-blockade showed similar enhancing effect on phagocytic indices and expressions of NOS and HSP70, particularly in double-blocked groups, although NO˙ production was found to be reduced in exercised animals submitted to both α- and β-blockade. Redox (glutathione) status and lipoperoxidation were evaluated in all test groups and approximately paralleled macrophage NO˙ production. We suggest the prevalence of a peripheral α1-adrenoreceptor inhibitory tonus that limits macrophage responsiveness but operates differently after physical exercise.
先前我们实验室的研究表明,单次适度运动可刺激巨噬细胞功能,通过核因子 kappa B 的激活来增加吞噬能力和产生过氧化氢和一氧化氮(NO˙)。在这项工作中,我们研究了α-和β-肾上腺素受体在静息和运动期间单核细胞/巨噬细胞功能中的作用。成年雄性 Wistar 大鼠在单次中等强度游泳运动前(腹部注射 100 μL/100 g)给予特定的肾上腺素能拮抗剂:哌唑嗪(α1-特异性拮抗剂 2 mg/kg)、普萘洛尔(非特异性β1/β2 拮抗剂 10 mg/kg)、双重阻断(α1 和β1/β2)或磷酸盐缓冲盐水(对照)。急性运动包括 60 分钟的中等强度单次游泳运动(胸部负重 5%体重)。对照组(休息)在给药后 60 分钟接受相同的拮抗剂并被处死。运动增加了吞噬能力(1.7 倍,p<0.05)、NO˙的产生(5.24 倍,p<0.001)和诱导型一氧化氮合酶(NOS2)的表达(增加 58.1%),从而提示巨噬细胞激活。β-肾上腺素受体阻断不会改变这种行为。然而,在休息的动物中,α1 拮抗剂,以及双重(α1/β)阻断,进一步增加了吞噬能力(高达 261%,p<0.001)、NO˙的产生(高达 328%,p<0.001)和 NOS2 的表达(增加 182%,p<0.001)和 HSP70(增加 42.5%,p<0.01),这表明α1 刺激对巨噬细胞激活具有紧张性抑制作用。在运动的动物中,α1 阻断在吞噬指数和 NOS 和 HSP70 的表达上显示出类似的增强作用,特别是在双重阻断组中,尽管在接受α-和β-阻断的运动动物中发现 NO˙的产生减少。在所有测试组中都评估了氧化还原(谷胱甘肽)状态和脂质过氧化,其与巨噬细胞 NO˙的产生大致平行。我们认为,外周α1-肾上腺素受体抑制性张力占主导地位,限制了巨噬细胞的反应性,但在运动后表现不同。