Journal of Applied Physiology
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J Appl Physiol 89: 1483-1490, 2000;
8750-7587/00 $5.00
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Vol. 89, Issue 4, 1483-1490, October 2000

Hindlimb unweighting alters endothelium-dependent vasodilation and ecNOS expression in soleus arterioles

William G. Schrage, Christopher R. Woodman, and M. Harold Laughlin

Departments of Physiology and Veterinary Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211

The purpose of this study was to test the hypothesis that endothelium-dependent dilation is impaired in soleus resistance arteries from hindlimb-unweighted (HLU) rats. Male Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 14) or weight-bearing control (Con, n = 14) conditions for 14 days. After the 14-day treatment period, soleus first-order (1A) arterioles were isolated and cannulated with micropipettes to assess vasodilator responses to an endothelium-dependent dilator, ACh (10-9-10-4 M), and an endothelium-independent dilator, sodium nitroprusside (SNP, 10-9-10-4 M). Arterioles from HLU rats were smaller than Con arterioles (maximal passive diameter = 140 ± 4 and 121 ± 4 µm in Con and HLU, respectively) but developed similar spontaneous myogenic tone (43 ± 3 and 45 ± 3% in Con and HLU, respectively). Arteries from Con and HLU rats dilated in response to increasing doses of ACh, but dilation was impaired in arterioles from HLU rats (P = 0.03), as was maximal dilation to ACh (85 ± 4 and 65 ± 4% possible dilation in Con and HLU, respectively). Inhibition of nitric oxide (NO) synthase (NOS) with Nomega -nitro-L-arginine (300 µM) reduced ACh dilation by ~40% in arterioles from Con rats and eliminated dilation in arterioles from HLU rats. The cyclooxygenase inhibitor indomethacin (50 µM) did not significantly alter dilation to ACh in either group. Treatment with Nomega -nitro-L-arginine + indomethacin eliminated all ACh dilation in Con and HLU rats. Dilation to sodium nitroprusside was not different between groups (P = 0.98). To determine whether HLU decreased expression of endothelial cell NOS (ecNOS), mRNA and protein levels were measured in single arterioles with RT-PCR and immunoblot analysis. The ecNOS mRNA and protein expression was significantly lower in arterioles from HLU rats than in Con arterioles (20 and 65%, respectively). Collectively, these data indicate that HLU impairs ACh dilation in soleus 1A arterioles, in part because of alterations in the NO pathway.

skeletal muscle; microcirculation; acetylcholine; microgravity; physical inactivity; indomethacin; Nomega -nitro-L-arginine


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