VASCULAR BIOLOGY AND SIMULATED MICROGRAVITY

后肢失重模型是一种用于模拟选择性条件下， 微重力 暴露于HU的大鼠表现出运动能力的降低 其特征在于最大摄氧量（VO 2 max）较低。 的 这种去适应效应的机制涉及受损的能力， 增加运动时骨骼肌血流量。 的总体目标 本研究旨在确定内皮依赖性血管扩张剂 反应在HU大鼠中受损。 此外，我们将确定是否 HU导致血管流动能力降低， 后肢的毛细血管交换 将讨论五个具体目标。 目标#1将确定HU对内皮细胞- 管道动脉中的依赖性血管舒张和微血管阻力 从足底肌和比目鱼肌分离的动脉。 目标#2将 测定HU对内皮细胞一氧化氮合酶表达的影响 氧化物合酶（ecNODS）在导管和阻力动脉。 目标#3将 测定HU对导管内皮细胞一氧化氮合酶mRNA含量及阻力的影响 动脉 目标4将确定ecNOS减少的时间过程 活性和mRNA水平。 目标5将确定暴露于HU是否 降低血管流动能力和毛细血管交换的可能性。 假设内皮依赖性血管舒张功能受损 在从暴露于HU的大鼠分离的血管中。

Hindlimb unweighing (HU) is a model used to simulate select condition of microgravity. Rats exposed to HU exhibit reductions in exercise capacity characterized by lower measures of maximal oxygen uptake (VO2 max). The mechanism for this deconditioning effect involves an impaired ability to increase skeletal muscle blood flow during exercise. The general aim of this study is to determine whether endothelium-dependent vasodilator responses are impaired in HU rats. In addition we will determine whether HU causes a decrease in vascular flow capacity and the potential for capillary exchange in the hindlimbs. Five specific aims will be addressed. Aim #1 will determine the effects of HU on the potential for endothelium- dependent vasodilation in a conduit artery and microvascular resistance arteries isolated from the plantaris and soleus muscles. Aim #2 will determine the effect of HU on the expression of endothelial cell nitric oxide synthase (ecNODS) in conduit and resistance arteries. Aim #3 will determine the effect of HU on ecNOS mRNA content in conduit and resistance arteries. Aim #4 will determine the time course of the reductions in ecNOS activity and mRNA levels. Aim #5 will determine whether exposure to HU reduces vascular flow capacity and the potential for capillary exchange. It is hypothesized that endothelium-dependent vasodilation will be impaired in vessels isolated from rats exposed to HU.