Quantification of Flow-Induced Vascular Adaptation Via an Organ Culture System

本研究的目的是验证一种假说，即应激介导的一氧化氮(NO)和内皮素-1(ET-1)的调节在调节由血流持续变化引起的颈动脉生长和重塑中起关键作用。这一假设将通过比较多个时间点(2小时、1天、3天、5天和7天)的形态、免疫组织化学和生物力学数据来验证：在四种情况下：对NO和ET-I的正常调节(即血管扩张或血管收缩)，以响应相同的流量增加或减少，或通过腺苷+NOS抑制剂的血管扩张或通过去甲肾上腺素+ETA受体阻滞剂的血管收缩。拟议项目的两个潜在的广泛结果是：(A)构建了一种新的计算机控制的体外活体小动脉脉动灌流系统，该系统能够进行7-10天的测试，以及(B)发展一种新的受限混合物理论，用于数学描述软组织的生长和重塑。两者都将是关键的进展，并将为未来的血管生物学和力学研究(包括对基因敲除小鼠模型的测试)提供一般的实验和理论基础。

0084644HumphreyThe objective of this research project is to test the hypothesis that stress-mediated regulation of nitric oxide (NO) and endothelin-I (ET-1) plays a key role in governing the growth and remodeling in carotid arteries that is induced by sustained alterations in blood flow. The hypothesis is to be examined by comparing morphological, immuno-histochemical, and biomechanical data at multiple time-points (I 2 hrs, 1, 3, 5 and 7 days) under four conditions: normal regulation of NO and ET- I (i.e., vasodilatation or vasoconstriction) in response to equal increases or decreases in flow versus equal vasodilation via adenosine plus a NOS-inhibitor or vasoconstriction via norepinephrine plus a ETA receptor blocker.Two potentially broad results of the proposed project are (a) the construction of a novel computer-controlled ex vivo pulsatile perfusion system for small arteries that enables testing for 7-10 days, and (b) development of a new theory of constrained mixtures for mathematically describing growth and remodeling in soft tissues. Both would be key advances, and together would provide a general experimental and theoretical foundation for future studies on vascular biology and mechanics (including tests on knockout mouse models).