Flow-Dependent Regulation of Vascular Function

Exactly sixty years ago Schretzenmayer provided the first experimental proof that changes in blood ftow can affect the diameter oflarge arteries. Since then, support has been growing for the idea that intraluminal blood ftow plays an important role in regulating not only the tone of blood vessels, but also their caliber and structure. Investigations of the&e phenomena have been given a strong impetus by the discovery that the endothelium can modulate the tone of underlying vascular smooth muscle via the release of a number of vasoactive substances. Investigators often diverge in their opinions regarding the nature of the vascular wall response to blood ftow and the mechanisms involved. This book is the first summary of our state of knowledge and the nature of the research carried out on ftow-related changes. Early chapters review involvement of shear-stress-dependent events in the circulation as a whole. They cover the biophysical principles of ftuid transport, the cellular signal transduction path- ways, and the molecular biology and biochemistry of ftow-induced changes in endothelial cells. Later chapters provide an in-depth summary of the regula- tion of vascular muscle tone by ftow. They include historical perspectives, evi- dence that ftow-induced vasodilation is primarily endothelium-dependent and that it can induce constriction, and details on ftow-dependent regulation in regional vascular beds. Several chapters emphasize the endothelial activation by shear stress and its importance in the control offtow in the microcirculation.