title: Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting.
abstract: The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (approximately 300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 microM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 300 microM) reduced flow-induced dilation by 65-70% in Con and HLU 1As. In contrast, L-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with L-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of L-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10(-9)-10(-4) M) in soleus 2As. L-NNA reduced ACh-induced dilation by approximately 40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment with L-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.
authors.affiliation: Department of Physiology, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Schrage
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Woodman
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D019417:Hindlimb Suspension / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D019001:Nitric Oxide Synthase / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D013314:Stress, Mechanical; D014664:Vasodilation; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine