ACETYLCHOLINE-INDUCED DILATION OF SOLEUS SECOND ORDER ARTERIOLES IN HINDLIMB UNWEIGHTED RATS
William G. Schrage, Christopher R. Woodman, M. Harold Laughlin · Medicine & Science in Sports & Exercise · 2001
Soleus blood flow is reduced at rest and during exercise after 14 days hindlimb unweighting (HLU). We tested the hypothesis that acetylcholine (ACh)-induced dilation is impaired in soleus arterioles isolated from HLU rats. Male Sprague-Dawley rats (∼300g) were exposed to HLU (n = 12) or weight bearing control (Con; n = 14) condition for 14 days. Soleus second order (2A) arterioles were isolated, cannulated, and subjected to increasing [ACh] (10−9–10−4 M). Arterioles from HLU rats exhibited smaller maximal passive diameter (Dmax) than Con rats (Con: 103 ± 4μm vs HLU: 87 ± 5μm, p < 0.02), and developed slightly less spontaneous tone (Con: 63 ± 3% Dmax vs HLU: 69 ± 2% Dmax, p < 0.05). ACh-induced dilation was not altered by HLU in absolute (p = 0.08) or relative terms (p = 0.22). Inhibition of nitric oxide synthase (NOS) with Nw-Nitro-L-Arginine (L-NNA; 300 μM) reduced dilation by ∼40% in Con rats and abolished ACh-induced dilation in HLU rats. The cycloxygenase (COX) inhibitor, indomethacin (Indo; 50 μM) did not alter ACh-induced dilation in either group. Combined treatment with L-NNA+Indo abolished dilation in Con rats and HLU rats. Responses to the endothelium-independent dilator, sodium nitroprusside (10−9–10−4 M), were similar between groups (p = 0.77). We conclude ACh-induced dilation in soleus 2A arterioles is not impaired by HLU, although the relative contribution of endothelial signaling pathways is altered. Specifically, HLU induces a shift from a NOS and COX interaction mediating ACh-induced dilation in Con rats, to a primary dependence on the NOS pathway in HLU rats. Supported by NASA 00-GSRP-045, NRSA-09739, and HL-36088.