VASCULAR BIOLOGY--EXERCISE TRAINING AND CORONARY DISEASE

冠心病（CHD）的发展是由中度 运动训练水平（EX）。 负责有益的 EX的影响尚不清楚。 本项目的核心主题 补助金（PPG）是EX由于训练而有益的假设- 引起冠状动脉血管功能的改变。 主要有3个 目的：A）阐明调控的细胞分子机制 血管平滑肌（VSM）和内皮在冠状动脉 循环，B）细胞/分子机制的系统测定 负责EX诱导的内在血管功能变化，以及 C）应用这种对血管细胞生物学的理解和EX- 诱导冠状动脉血管适应CHD的实验模型。 的 PPG正式确定并扩大了正在进行的广泛合作， 这个研究团队。一种综合的实验方法， 冠状动脉血管功能在整个冠状动脉树的久坐和 猪来了。 项目1和2重点关注管道冠状动脉的VSM 动脉 项目1采用电生理学和成像技术， 研究负责适应的细胞/分子机制， 肌浆网Ca ~（2+）释放和Ca ~（2+）挤出。 项目 2将检验EX诱导VSM跨膜变化的假设 信号传导机制和/或受体/第二信使途径。 项目3和4侧重于微循环。 项目3审查 血管阻力的控制和负责EX诱导的机制 成肌反应性和内皮介导的反应性的变化， 冠状动脉阻力 项目4将确定机制 负责EX诱导的经血管交换变化， 分离的微血管和直接测量不同的渗透性 大小的探针，有和没有血管扩张剂。 项目5旨在 研究EX诱导的冠状动脉血管适应性对 CHD模型 重点是EX对反应性的潜在影响 并将确定是否 EX可钝化慢性缺血引起的血管功能障碍。 完成 拟议的研究将大大提高对以下问题的理解： 血管细胞生物学，EX-induced冠状动脉血管 适应性，血流控制和血管交换的整合，以及 与CHD的互动 这种多层次的研究方法， EX后的冠状动脉血管功能代表了一个新的前沿， 运动生理学，有可能改变前- 在冠状循环中诱导适应。

The development of coronary heart disease (CHD) is blunted by moderate levels of exercise training (EX). Mechanisms responsible for beneficial effects of EX are not known. The central theme of this Program Project Grant (PPG) is the hypothesis that EX is beneficial due to training- induced alterations in coronary vascular function. There are 3 major goals: A) elucidation of cellular molecular mechanisms for regulation of vascular smooth muscle (VSM) and endothelium in the coronary circulation, B) systematic determination of cellular/molecular mechanisms responsible for EX-induced changes in intrinsic vascular function, and C) application of this understanding of vascular cell biology and EX- induced coronary vascular adaptation to experimental models of CHD. The PPG formalizes and expands extensive collaborative efforts ongoing among this research team. An integrated experimental approach that examines coronary vascular function throughout the coronary tree of sedentary and EX pigs is presented. Projects 1 and 2 focus on VSM of conduit coronary arteries. Project 1 employs electrophysiology and imaging techniques to examine cellular/molecular mechanisms responsible for adaptations in sarcoplasmic reticulum Ca2+ release and Ca2+ extrusion in VSM. Project 2 will test the hypothesis that EX induces changes in VSM transmembrane signalling mechanisms and/or receptor/second messenger pathways. Projects 3 and 4 focus on the microcirculation . Project 3 examines control of vascular resistance and mechanisms responsible for EX-induced changes in myogenic reactivity and endothelium-mediated responses of coronary resistance arteries. Project 4 will determine mechanisms responsible for EX-induced changes in transvascular exchange using isolated microvessels and direct measures of permeability to different sized probes with and without vasodilators. Project 5 is designed to investigate the impact of EX-induced coronary vascular adaptations on a model of CHD. The focus is on the potential effects of EX on reactivity of vessels in collateral dependent myocardium and will determine whether EX blunts vascular dysfunction caused by chronic ischemia. Completion of the proposed research will dramatically improve understanding of: vascular cell biology, mechanisms of EX-induced coronary vascular adaptation, integration of blood flow control and vascular exchange, and interactions with CHD. This multi-level approach to the study of coronary vasomotor function after EX represents a new frontier in exercise physiology that holds the potential to transform concepts of EX- induced adaptation in the coronary circulation.