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

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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).