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

0084644 Humphrey本研究项目的目的是检验以下假设：应激介导的一氧化氮（NO）和内皮素-I（ET-1）调节在控制由血流持续改变诱导的颈动脉生长和重塑中起关键作用。通过比较在四种条件下多个时间点（1 - 2小时、1、3、5和7天）的形态学、免疫组织化学和生物力学数据来检验该假设：NO和ET-1的正常调节（即，血管舒张或血管收缩），与通过腺苷加NOS抑制剂的相等血管舒张或通过去甲肾上腺素加ETA受体阻断剂的相等血管收缩相比。所提出的项目的两个潜在的广泛结果是（a）构建用于小动脉的新型计算机控制的离体脉动灌注系统，其能够进行7-10天的测试，和（B）发展用于数学描述软组织中的生长和重塑的约束混合物的新理论。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).