title: Effects of hindlimb unloading and ionizing radiation on skeletal muscle resistance artery vasodilation and its relation to cancellous bone in mice.
abstract: 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.
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware;
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Prisby
authors.affiliation: Space Biosciences Division, NASA Ames Research Center, Moffett Field, California;
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Alwood
authors.affiliation: Department of Applied Physiology and Kinesiology and the Center for Exercise Science, University of Florida, Gainesville, Florida; Department of Kinesiology and the Johnson Cancer Research Center, Kansas State University, Manhattan, Kansas; and.
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Behnke
authors.affiliation: Department of Applied Physiology and Kinesiology and the Center for Exercise Science, University of Florida, Gainesville, Florida;
authors.forename: John N
authors.initials: JN
authors.lastname: Stabley
authors.affiliation: Department of Applied Physiology and Kinesiology and the Center for Exercise Science, University of Florida, Gainesville, Florida;
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: McCullough
authors.affiliation: Department of Applied Physiology and Kinesiology and the Center for Exercise Science, University of Florida, Gainesville, Florida; Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, Florida.
authors.forename: Payal
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Space Biosciences Division, NASA Ames Research Center, Moffett Field, California;
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Globus
authors.affiliation: Department of Applied Physiology and Kinesiology and the Center for Exercise Science, University of Florida, Gainesville, Florida; Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, Florida mdelp@fsu.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019417:Hindlimb Suspension / Q000379:methods; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011839:Radiation, Ionizing; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D014893:Weightlessness
chemical_list: D006834:Hydrazines; D014665:Vasodilator Agents; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine
keywords: bone remodeling; endothelium-dependent vasodilation; microgravity; radiation; spaceflight