The interaction of the endothelium with blood and its elements, circulating factors, and its active metabolic state make it an attractive target for therapeutic alterations. The location of the endothelium between blood and vascular smooth muscle is ideal for the endothelium to serve as a fine transducer of mechanical and chemical forces. Endothelial dysfunction occurs in several diseases. Many endogenous regulatory responses, such as distribution of blood flow, hemostasis, and vasomotor tone, are controlled by endothelial-derived factors. Thus, exogenous modulation of such endothelial factors is a desirable goal.

The physiological importance of the endothelium in homeostatic function has been recognized since the discovery of endothelial-derived relaxing factor (EDRF), which was later found to be endothelial-derived nitric oxide (NO). The actions of NO on adjacent endothelial cells (ECs), other circulating cells, and on adjacent myocytes make NO a valuable primaryor secondary messenger of innumerablephysiologicprocesses. Signal transduction and the importance of endothelialderived NO and inducible NO in inflammatory processes are reviewed here. This chapter further aims to review primary methods of endothelial stimulation in vivo and therapeutic methods used in the past and currently to alter endothelial responses. Unlike pharmacologic interventions in which drug dosing, local availability, distribution, and side effects can outweigh the potential beneficial effects of the drug, stimulating the endothelium to produce beneficial factors has several advantages: (a) the endothelium is present in every organ, (b) actions are local, and (c) there is virtually no potential for overdosing or toxic effects.

HEMODYNAMIC FACTORS RESPONSIBLE FOR ENDOTHELIAL OUTPUT

The frictional force engendered on the vascular endothelium by the flowing, viscous blood is termed hemodynamic shear stress.