Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance arteries in mice

作者：Stabley John N; Dominguez James M II; Dominguez Catherine E; Solis Fredy R Mora; Ahlgren Joslyn; Behnke Bradley J; Muller Delp Judy M; Delp Michael D^*

来源：Journal of Applied Physiology, 2012, 113(9): 1439-1445.

DOI：10.1152/japplphysiol.00772.2012

• spaceflight
• microgravity
• vasoconstriction
• skeletal muscle
• c57bl/6 mice
• orthostatic intolerance

Stabley JN, Dominguez JM 2nd, Dominguez CE, Solis FR, Ahlgren J, Behnke BJ, Muller-Delp JM, Delp MD. Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance arteries in mice. J Appl Physiol 113: 1439-1445, 2012. First published September 13, 2012; doi:10.1152/japplphysiol.00772.2012.-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 Ca2+ 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 Ca2+ 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.

• 出版日期2012-11