Journal
JOURNAL OF APPLIED PHYSIOLOGY
Volume 120, Issue 2, Pages 97-106Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00423.2015
Keywords
radiation; spaceflight; endothelium-dependent vasodilation; microgravity; bone remodeling
Categories
Funding
- National Space and Biomedical Research Institute [MA02501]
- National Aeronautics and Space Administration (NASA) Space Biology [NNX12AL41G, NNX14AQ57G]
- NASA Postdoctoral Program
- American Cancer Society [RSG-14-150-01-CCE]
- NASA [NNX14AQ57G, 674317, 69594, NNX12AL41G] Funding Source: Federal RePORTER
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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 Cs-137), and HU-Rad (15-day tail suspension and 200 cGy of Cs-137). 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). Endotheliumin-dependent 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 PGI(2)-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.
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