Butler P J, Weinbaum S, Chien S, Lemons D E
Department of Mechanical Engineering, The City College of New York, New York 10031, USA.
Microcirculation. 2000 Feb;7(1):53-65.
To quantify the relative contributions of the rate of change and the magnitude of shear stress to endothelium-mediated arteriolar dilation.
A feedback control system was designed in which shear stress (tau) and the temporal shear gradient (TSG) were prescribed and dynamically controlled in isolated rat cremaster 1A arterioles. The TSG was the quotient of the maximum shear stress and the ramp duration. This system was used to assess the roles of tau and TSG in the initial, transient vasodilations and the secondary, sustained vasodilations in response to steps and ramps in shear stress.
Both step- and ramp-shear experiments revealed time-dependent hiphasic vasodilations that we report for the first time. Application of a step-shear stress of 20 dynes/cm2 elicited an initial transient vasodilation that peaked at about 4 min. When the shear stress was applied as a ramp that reached the maximum value of 20 dynes/cm2 over 5 min, a vasodilation was observed over the ramp period, which reached a peak at the end of the ramp period that was much lower than that observed after step shear. After 20 dynes/cm2 was attained, the vessel diameter decreased despite constant maintenance of the maximum shear stress. In both step- and ramp-shear experiments, after the decrease of the initial vasodilation, a second phase of vasodilation began approximately 15 min after the beginning of the shear application. The second phase of vasodilation reached a steady state that was essentially the same for both the step and the ramp shear. By refining the ramping apparatus further, we varied the TSG up to 40 dynes/cm2 per second and showed that the early vasodilation was highly rate sensitive to TSGs greater than 5 dynes/cm2 per second for a given intermediate value of final shear stress (20 dynes/cm2) and was magnitude sensitive when shear was increased gradually (TSG < 5 dynes/cm2 per second).
Our results suggest that two fundamentally different responses to shear stress are mediated by microvascular endothelium: one vasodilation is elicited by shear stress changes on a time scale of a few seconds or less and another is elicited by shear stress changes on a longer time scale. The former response is potent, transient, and rate sensitive; the latter is more modest, sustained, and magnitude sensitive.
量化变化率和剪切应力大小对内皮介导的小动脉舒张的相对贡献。
设计了一个反馈控制系统，在该系统中，在离体大鼠提睾肌1A小动脉中规定并动态控制剪切应力（τ）和瞬时剪切梯度（TSG）。TSG是最大剪切应力与斜坡持续时间的商。该系统用于评估τ和TSG在响应剪切应力的阶跃和斜坡时初始、短暂的血管舒张以及继发、持续的血管舒张中的作用。
阶跃剪切和斜坡剪切实验均揭示了我们首次报道的随时间变化的双相血管舒张。施加20达因/平方厘米的阶跃剪切应力会引起初始短暂的血管舒张，在约4分钟时达到峰值。当剪切应力以斜坡形式施加，在5分钟内达到20达因/平方厘米的最大值时，在斜坡期观察到血管舒张，在斜坡期末达到峰值，该峰值远低于阶跃剪切后观察到的峰值。在达到20达因/平方厘米后，尽管最大剪切应力保持恒定，血管直径仍减小。在阶跃剪切和斜坡剪切实验中，初始血管舒张降低后，在施加剪切力开始约15分钟后开始了血管舒张的第二阶段。血管舒张的第二阶段达到稳态，对于阶跃剪切和斜坡剪切基本相同。通过进一步改进斜坡装置，我们将TSG变化至每秒40达因/平方厘米，并表明对于给定的最终剪切应力中间值（20达因/平方厘米），早期血管舒张对大于每秒5达因/平方厘米的TSG高度敏感，而当剪切力逐渐增加时（TSG<每秒5达因/平方厘米）对大小敏感。
我们的结果表明，微血管内皮对剪切应力有两种根本不同的反应：一种血管舒张是由几秒或更短时间尺度上的剪切应力变化引起的，另一种是由更长时间尺度上的剪切应力变化引起的。前一种反应强烈、短暂且对速率敏感；后一种反应较为温和、持续且对大小敏感。
