Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance arteries in mice. 2012

John N Stabley, and James M Dominguez, and Catherine E Dominguez, and Fredy R Mora Solis, and Joslyn Ahlgren, and Bradley J Behnke, and Judy M Muller-Delp, and Michael D Delp
Department of Applied Physiology and Kinesiology and Center for Exercise Science, University of Florida, Gainesville, Florida 32611, USA.

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.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001158 Arteries The vessels carrying blood away from the heart. Artery
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013026 Space Flight Travel beyond the earth's atmosphere. Space Exploration,Space Travel,Spaceflight,Exploration, Space,Explorations, Space,Flight, Space,Flights, Space,Space Explorations,Space Flights,Space Travels,Spaceflights,Travel, Space,Travels, Space
D014661 Vasoconstriction The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE. Vasoconstrictions
D014893 Weightlessness Condition in which no acceleration, whether due to gravity or any other force, can be detected by an observer within a system. It also means the absence of weight or the absence of the force of gravity acting on a body. Microgravity, gravitational force between 0 and 10 -6 g, is included here. (From NASA Thesaurus, 1988) Microgravity,Zero Gravity,Gravity, Zero
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053498 Sarcoplasmic Reticulum Calcium-Transporting ATPases Calcium-transporting ATPases that catalyze the active transport of CALCIUM into the SARCOPLASMIC RETICULUM vesicles from the CYTOPLASM. They are primarily found in MUSCLE CELLS and play a role in the relaxation of MUSCLES. Calcium-Transporting ATPases, Sarcoplasmic Reticulum,Sarcoplasmic Reticulum Calcium ATPase,SERCA Calcium ATPase,SERCA1 Calcium ATPase,SERCA2 Calcium ATPase,SERCA2a Calcium ATPase,SERCA3 Calcium ATPase,SR Ca(2+)-ATPase 1,SR Ca(2+)-ATPase 2,SR Ca(2+)-ATPase 3,Sarco-Endoplasmic Reticulum Ca2+-ATPase,Sarcoplasmic Reticulum Ca(2+)-ATPase,Sarcoplasmic Reticulum Calcium-Transporting ATPase 1,Sarcoplasmic Reticulum Calcium-Transporting ATPase 2,Sarcoplasmic Reticulum Calcium-Transporting ATPase 2a,Sarcoplasmic Reticulum Calcium-Transporting ATPase 3,Sarcoplasmic-Endoplasmic Reticulum Calcium ATPase 2,Sarcoplasmic-Endoplasmic Reticulum Calcium ATPase 2a,Sarcoplasmic-Endoplasmic Reticulum Calcium ATPase 3,Sarcoplasmic-endoplasmic Reticulum Calcium ATPase 1,Ca2+-ATPase, Sarco-Endoplasmic Reticulum,Calcium Transporting ATPases, Sarcoplasmic Reticulum,Reticulum Ca2+-ATPase, Sarco-Endoplasmic,Sarco Endoplasmic Reticulum Ca2+ ATPase,Sarcoplasmic Endoplasmic Reticulum Calcium ATPase 2,Sarcoplasmic Endoplasmic Reticulum Calcium ATPase 2a,Sarcoplasmic Endoplasmic Reticulum Calcium ATPase 3,Sarcoplasmic Reticulum Calcium Transporting ATPase 1,Sarcoplasmic Reticulum Calcium Transporting ATPase 2,Sarcoplasmic Reticulum Calcium Transporting ATPase 2a,Sarcoplasmic Reticulum Calcium Transporting ATPase 3,Sarcoplasmic Reticulum Calcium Transporting ATPases,Sarcoplasmic endoplasmic Reticulum Calcium ATPase 1

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