Control Mechanisms of Vascular Endothelial Function

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Control of blood vessels is key to regulating the cardiovascular system. The cells that make up the blood vessels (endothelial cells and vascular smooth muscle cells) produce and release a number of substances that control the function of the arteries. In particular, the endothelial cells produce both Endothelium-Derived Relaxing Factors (EDRFs) and Contracting Factors (EDCFs) that control how arteries relax and contract to regulate blood flow. It is necessary to discover how these factors are produced and how they control blood vessel function. One possible 'master regulator' could be a molecule called AMP-activated protein kinase (AMPK). Very little is known regarding how AMPK affects artery function, but the proposed research will discover ways in which AMPK affects EDRF and EDCF activity and vascular function. Our experimental approach uses intact rats and arteries isolated from rats. Different types of blood vessels with normal and dysfunctional endothelium will be used to better understand the factors controlling AMPK, and EDRF/EDCF balance. Another unique feature of this work is that we will also study adaptations in the factors controlling EDRF and EDCF activity to exercise training. This is important because although there is a well-established beneficial effect of exercise on artery function, the changes in the artery cells that make this possible are not known. This research is important in order to understand the basic mechanisms controlling artery function, and why artery function changes in response to a number of stresses. Thus, the research will be most immediately of interest to biologists and vascular physiologists. It is anticipated that, because many of the signals being studied are of importance in a variety of other tissues and conditions as well, that many of the results will be of widespread interest and importance to scientists around the world. This basic science understanding, and potential for it to be translated into applications by clinical researchers make the research of interest and importance to Canadians.