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.

小动脉重塑可能涉及平滑肌细胞（SMC）直径依赖性力生成能力的转变。本研究旨在探究该收缩塑性发生的程度及其条件。将大鼠肠系膜动脉固定于等长肌力计上。在100毫米汞柱的压力下，经过16小时或40小时的刺激，于被动直径的40%或110%处，确定了活性直径-张力关系。在40%的条件下，16小时的内皮素-1（ET-1）孵育而非U46619，使得力生成能力向较小的直径转变。炎症细胞因子（TNF-α、IL-1β、IFN-γ）、TGF-β或血清均未引起此类转变，也未增强ET-1的作用。ET-1介导的变化不受超氧化物歧化酶和过氧化氢酶的影响。在ET-1存在的情况下，向内基质重塑的速度减慢，发生在40小时后。维持在110%的动脉，其力生成能力向较大直径的转变被ET-1所阻止，但不是U46619。在活性而非被动状态下，SMC在40%孵育后核长度发生了改变。这些数据表明，在小动脉中存在收缩塑性，其中慢性应变是外驱动力，而特定的ET-1则是内驱动力，其作用机制似乎与氧化应激、炎症途径或SMC的主要重塑无关。