title: Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance arteries in mice.
abstract: Cardiovascular adaptations to microgravity undermine the physiological capacity to respond to orthostatic challenges upon return to terrestrial gravity. The purpose of the present study was to investigate the influence of spaceflight on vasoconstrictor and myogenic contractile properties of mouse gastrocnemius muscle resistance arteries. We hypothesized that vasoconstrictor responses acting through adrenergic receptors [norepinephrine (NE)], voltage-gated Ca(2+) channels (KCl), and stretch-activated (myogenic) mechanisms would be diminished following spaceflight. Feed arteries were isolated from gastrocnemius muscles, cannulated on glass micropipettes, and physiologically pressurized for in vitro experimentation. Vasoconstrictor responses to intraluminal pressure changes (0-140 cmH(2)O), KCl (10-100 mM), and NE (10(-9)-10(-4) M) were measured in spaceflown (SF; n = 11) and ground control (GC; n = 11) female C57BL/6 mice. Spaceflight reduced vasoconstrictor responses to KCl and NE; myogenic vasoconstriction was unaffected. The diminished vasoconstrictor responses were associated with lower ryanodine receptor-2 (RyR-2) and ryanodine receptor-3 (RyR-3) mRNA expression, with no difference in sarcoplasmic/endoplasmic Ca(2+) ATPase 2 mRNA expression. Vessel wall thickness and maximal intraluminal diameter were unaffected by spaceflight. The data indicate a deficit in intracellular calcium release via RyR-2 and RyR-3 in smooth muscle cells as the mechanism of reduced contractile activity in skeletal muscle after spaceflight. Furthermore, the results suggest that impaired end-organ vasoconstrictor responsiveness of skeletal muscle resistance arteries contributes to lower peripheral vascular resistance and less tolerance of orthostatic stress in humans after spaceflight.
authors.affiliation: Department of Applied Physiology and Kinesiology and Center for Exercise Science, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Stabley
authors.forename: James M
authors.initials: JM
authors.lastname: Dominguez
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Dominguez
authors.forename: Fredy R
authors.initials: FR
authors.lastname: Mora Solis
authors.forename: Joslyn
authors.initials: J
authors.lastname: Ahlgren
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Behnke
authors.forename: Judy M
authors.initials: JM
authors.lastname: Muller-Delp
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply*; D054971:Orthostatic Intolerance / Q000209:etiology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D013026:Space Flight; D014661:Vasoconstriction / Q000502:physiology*; D014893:Weightlessness / Q000009:adverse effects
chemical_list: D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse