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Departments of 1 Anesthesiology and Critical Care Medicine and 2 Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287
Vascular contractile
hyporesponsiveness is an important mechanism underlying orthostatic
intolerance after microgravity. Baroreceptor reflexes can
modulate both pulmonary resistance and capacitance function and thus
cardiac output. We hypothesized, therefore, that pulmonary
vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model
of microgravity. Pulmonary artery (PA) contractile responses to
phenylephrine (PE) and U-46619 (U4) were significantly decreased in the
PAs from HLU vs. control (C) animals.
NG-nitro-L-arginine methyl ester
(10
5 M) enhanced the contractile responses in the PA
rings from both C and HLU animals and completely abolished the
differential responses to PE and U4 in HLU vs. C animals.
Vasorelaxant responses to ACh were significantly enhanced in PA rings
from HLU rats compared with C. Moreover, vasorelaxant responses to
sodium nitroprusside were also significantly enhanced. Endothelial
nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression
were significantly enhanced in PA and lung tissue from HLU rats. In
marked contrast, the expression of inducible nitric oxide synthase was
unchanged in lung tissue. These data support the hypothesis that
vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.
hindlimb unweighting; orthostatic intolerance; nitric oxide synthase; vasodilation; endothelium
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