Price R J, Skalak T C
Department of Biomedical Engineering, University of Virginia, Charlottesville 22908, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):H752-9. doi: 10.1152/ajpheart.1996.271.2.H752.
The arteriolar network undergoes structural adaptation in several physiological and pathological conditions, including exercise, maturation, hypertension, and reduced tissue perfusion due to arterial ligation. Although many physical and biochemical stimuli for arteriolar adaptation have been proposed, the individual contributions of these specific stimuli have yet to be elucidated. We tested the hypothesis that hemodynamic stress is an important determinant of growth and remodeling in the arteriolar network. An immunofluorescence, dual-labeling technique for the smooth muscle (SM) contractile proteins SM alpha-actin and SM myosin heavy chain (MHC) was used to assess terminal and arcade arteriolar (AA) remodeling in the rat gracilis muscle arteriolar network in response to chronic vasodilation, a stimulus that elevates circumferential wall stress levels in the arterioles and capillaries. SM alpha-actin, a marker of SM from the earliest stages of differentiation, was used to delineate the terminal and AAs. SM-MHC, a marker of SM in later stages of differentiation, was used to assess the relative maturity state of SM in terminal arteriolar endings. Mean percentage of SM-MHC negative terminal arteriolar endings per muscle, a measure of terminal arteriolar development, increased from 37.6 to 56.0% after 1 wk of prazosin treatment and from 36.3 to 57.6% after 2 wk of treatment. Mean number of AA segments with diameters < 15 microns increased more than threefold from 1.25 to 5.25 after 2 wk, consistent with the formation of new AA segments by the anastomoses of small-diameter terminal arterioles. Because arteriolar remodeling proceeded in a network pattern that has been shown to be consistent with a circumferential wall stress-growth rule and inconsistent with a wall shear stress-growth rule, the experimental results suggest that circumferential wall stress is a stimulus for arteriolar network remodeling.
在多种生理和病理状况下，包括运动、成熟、高血压以及因动脉结扎导致的组织灌注减少，小动脉网络会发生结构适应性变化。尽管已经提出了许多促使小动脉适应的物理和生化刺激因素，但这些特定刺激因素各自的作用尚未阐明。我们检验了这样一个假说，即血流动力学应激是小动脉网络生长和重塑的重要决定因素。采用免疫荧光双标记技术检测平滑肌（SM）收缩蛋白SMα - 肌动蛋白和SM肌球蛋白重链（MHC），以评估大鼠股薄肌小动脉网络中终末小动脉和弓状小动脉（AA）对慢性血管舒张的重塑反应，慢性血管舒张是一种能提高小动脉和毛细血管周向壁应力水平的刺激。SMα - 肌动蛋白是平滑肌从分化早期阶段开始的标志物，用于描绘终末小动脉和弓状小动脉。SM - MHC是平滑肌分化后期阶段的标志物，用于评估终末小动脉末梢平滑肌的相对成熟状态。每块肌肉中SM - MHC阴性终末小动脉末梢的平均百分比（一种终末小动脉发育的指标）在哌唑嗪治疗1周后从37.6%增加到56.0%，治疗2周后从36.3%增加到57.6%。直径<15微米的弓状小动脉段的平均数量在2周后从1.25增加到5.25，增加了三倍多，这与小直径终末小动脉吻合形成新的弓状小动脉段一致。由于小动脉重塑以一种网络模式进行，这种模式已被证明与周向壁应力 - 生长规则一致，而与壁切应力 - 生长规则不一致，实验结果表明周向壁应力是小动脉网络重塑的一种刺激因素。
