Supplementary Material for: Smooth Muscle Contractile Plasticity in Rat Mesenteric Small Arteries: Sensitivity to Specific Vasoconstrictors, Distension and Inflammatory Cytokines

Small artery remodeling may involve a shift in the diameter-dependent force generating capacity of smooth muscle cells (SMC). We tested to what extent and under which conditions such contractile plasticity occurs. Rat mesenteric arteries were mounted on isometric myographs. Active diameter-tension relations were determined after application of several stimuli for 16 or 40 h at 40 or 110% of the passive diameter at 100 mm Hg. At 40%, 16-hour incubation with endothelin-1 (ET-1) but not U46619 shifted force capacity towards smaller diameters. Inflammatory cytokines (TNF-α, IL-1β, IFN-γ), TGF-β or serum neither induced such shift nor augmented the effect of ET-1. The ET-1-mediated change was not affected by superoxide dismutase and catalase. Inward matrix remodeling in the presence of ET-1 was slower, occurring after 40 h. Arteries maintained at 110% showed a shift of force capacity to larger diameters, which was prevented by ET-1 but not by U46619. In the active but not the passive state, SMC had altered nuclear lengths after incubation at 40%. These data demonstrate contractile plasticity in small arteries, where chronic strain is an outward drive and specifically ET-1 an inward drive, acting through mechanisms that do not seem to relate to oxidative stress, inflammatory pathways or major reorganization of the SMC.

小动脉重构可能伴随平滑肌细胞（smooth muscle cells, SMC）的直径依赖性肌力生成能力发生改变。本研究旨在探究此类收缩可塑性的发生程度与所需条件。将大鼠肠系膜动脉固定于等长肌张力描记器（isometric myographs）上，在100mmHg下以对应被动直径40%或110%的条件施加多种刺激16或40小时后，测定标本的主动直径-张力关系。当标本处于40%被动直径条件时，经内皮素-1（endothelin-1, ET-1）孵育16小时可使肌力生成能力向更小直径方向偏移，而U46619无此效应。炎性细胞因子（肿瘤坏死因子-α、白细胞介素-1β、干扰素-γ）、转化生长因子-β（transforming growth factor-β, TGF-β）或血清既未诱导此类肌力偏移，也未增强ET-1的作用。ET-1介导的肌力变化不受超氧化物歧化酶与过氧化氢酶的影响。在ET-1存在时发生的内向性基质重构进程较为缓慢，于40小时后才出现。维持于110%被动直径的动脉标本，其肌力生成能力向更大直径方向偏移，该效应可被ET-1阻断，但U46619无此阻断作用。仅在收缩活性状态而非静息被动状态下，经40%被动直径条件孵育的SMC会出现核长度改变。本研究数据证实小动脉存在收缩可塑性：慢性牵张为外向性驱动因素，而ET-1为内向性驱动因素，其作用机制似乎与氧化应激、炎性通路或SMC的大规模重组无关。