Prisby Rhonda D, Alwood Joshua S, Behnke Brad J, Stabley John N, McCullough Danielle J, Ghosh Payal, Globus Ruth K, Delp Michael D
Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware;
Space Biosciences Division, NASA Ames Research Center, Moffett Field, California;
J Appl Physiol (1985). 2016 Jan 15;120(2):97-106. doi: 10.1152/japplphysiol.00423.2015. Epub 2015 Oct 15.
Spaceflight has profound effects on vascular function as a result of weightlessness that may be further compounded by radiation exposure. The purpose of the present study was to assess the individual and combined effects of hindlimb unloading (HU) and radiation (Rad) on vasodilator responses in the skeletal muscle vasculature. Adult male C57BL/6J mice were randomized to one of four groups: control (Con), HU (tail suspension for 15 days), Rad (200 cGy of (137)Cs), and HU-Rad (15-day tail suspension and 200 cGy of (137)Cs). Endothelium-dependent vasodilation of gastrocnemius feed arteries was assessed in vitro using acetylcholine (ACh, 10(-9)-10(-4) M) and inhibitors of nitric oxide synthase (NOS) and cyclooxygenase (COX). Endothelium-independent vasodilation was assessed using Dea-NONOate (10(-9)-10(-4) M). Endothelium-dependent and -independent vasodilator responses were impaired relative to Con responses in all treatment groups; however, there was no further impairment from the combination of treatments (HU-Rad) relative to that in the HU and Rad groups. The NOS-mediated contribution to endothelium-dependent vasodilation was depressed with HU and Rad. This impairment in NOS signaling may have been partially compensated for by an enhancement of PGI2-mediated dilation. Changes in endothelium-dependent vasodilation were also associated with decrements in trabecular bone volume in the proximal tibia metaphysis. These data demonstrate that the simulated space environment (i.e., radiation exposure and unloading of muscle and bone) significantly impairs skeletal muscle artery vasodilation, mediated through endothelium-dependent reductions in NOS signaling and decrements in vascular smooth muscle cell responsiveness to NO.
由于失重，太空飞行对血管功能有深远影响，而辐射暴露可能会使这种影响进一步加剧。本研究的目的是评估后肢卸载（HU）和辐射（Rad）对骨骼肌血管系统血管舒张反应的单独及联合作用。成年雄性C57BL/6J小鼠被随机分为四组之一：对照组（Con）、HU组（尾部悬吊15天）、Rad组（200 cGy的¹³⁷Cs）和HU-Rad组（15天尾部悬吊和200 cGy的¹³⁷Cs）。使用乙酰胆碱（ACh，10⁻⁹ - 10⁻⁴ M）以及一氧化氮合酶（NOS）和环氧化酶（COX）抑制剂，在体外评估腓肠肌供血动脉的内皮依赖性血管舒张。使用二乙胺NONOate（10⁻⁹ - 10⁻⁴ M）评估非内皮依赖性血管舒张。相对于Con组的反应，所有治疗组的内皮依赖性和非内皮依赖性血管舒张反应均受损；然而，与HU组和Rad组相比，联合治疗组（HU-Rad）并未出现进一步的损害。HU和Rad使NOS介导的内皮依赖性血管舒张作用减弱。NOS信号传导的这种损害可能已通过PGI₂介导的舒张增强得到部分补偿。内皮依赖性血管舒张的变化也与胫骨近端干骺端小梁骨体积的减少有关。这些数据表明，模拟太空环境（即辐射暴露以及肌肉和骨骼卸载）通过内皮依赖性地降低NOS信号传导和血管平滑肌细胞对NO的反应性，显著损害骨骼肌动脉血管舒张。
