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Effects of hindlimb unloading and radiation on vasodilator responses in skeletal muscle arteries (1106.18)
Author(s) -
Ghosh Payal,
Stabley John,
Kilar Cody,
Behnke Bradley,
Alwood Joshua,
Shirazi Yasaman,
Globus Ruth,
Delp Michael
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1106.18
Subject(s) - vasodilation , hindlimb , spaceflight , endothelium , skeletal muscle , medicine , microcirculation , nitric oxide , gastrocnemius muscle , vasoconstriction , endocrinology , engineering , aerospace engineering
Long‐term spaceflight leads to extensive changes to the microvasculature as a result of weightlessness, which may be compounded by the effects of radiation exposure. The purpose of this study was to assess the individual and combined effects of hindlimb unloading (HU) and radiation (Rad) on vasodilator responses in the skeletal muscle microcirculation. Adult male C57BL/6 mice were randomized to one of four groups: control, HU (tail suspension for 10‐11 days), Rad (100cGy of 150MeV protons and 20cGy of 800MeV 56 Fe), and HU‐Rad. Gastrocnemius feed arteries were isolated, cannulated and pressurized for in vitro study. Endothelium‐dependent (ACh, 10 ‐9 ‐10 ‐4 M) and ‐independent (Dea‐NONOate, 10 ‐9 ‐10 ‐4 M) vasodilator responses were evaluated. NOS and COX inhibitors (L‐NAME and Indomethacin) were used to determine which endothelium‐dependent signaling pathways were altered. In all treatment groups endothelium‐dependent and ‐independent vasodilator responses were significantly impaired compared to controls (max ACh dilation: 91±2%). ACh‐induced vasodilation was less in the HU‐Rad (68±3%) group than in HU (79±1%) or Rad (80±2%) alone. Independent and simultaneous treatment with L‐NAME and indomethacin reduced vasodilation and eliminated group differences. Dea‐NONOate‐induced vasodilation was reduced to a greater degree in the Rad and HU‐Rad groups. These findings suggest that the combination of insults experienced during spaceflight lead to significant impairment of vasodilatory function, mediated through endothelium‐dependent reductions in NOS signaling and vascular smooth muscle dysfunction. Grant Funding Source : Supported by NSBRI, NCC 9‐58‐44