Today's human body was “designed,” through natural selection, to maximize fitness in the early ancestral environment, a time in which physical activity was obligatory for survival (see Chapter 16).As an important corollary, the human body is not ideally suited for the modernWestern lifestyle, where inactivity is the norm. Indeed, physical inactivity is now established as an independent risk factor for cardiovascular morbidity and mortality, an effect that is similar to that of high blood pressure, high levels of blood lipids, and smoking combined (1). An important prerequisite for reversing this trend and prolonging life is to encourage a change in societal attitude such that physical activity, and not a sedentary lifestyle, is viewed as the physiological and behavioral norm. Indeed, exercise training results in reduced primary and secondary vascular events, independent of amelioration of other cardiac risk factors. Exercise is associatedwith significant physiological adaptations in many systems, including skeletal, muscle, heart, metabolism, and the vasculature. Central to the protective effect of exercise on endothelium is increased bioavailability of nitric oxide (NO), achieved through increased production of NO and decreased reactive oxygen species (ROS)–mediated inhibition of NO activity. The goals of this chapter are to describe some of the long- and short-termadaptations to exercise in the blood vessel endothelium, to review potential intracellular signaling pathways and other molecular mechanisms associated with these adaptations and to relate these changes to integrated performance and health effects.

ENDOTHELIAL FUNCTION

The endothelium was previously regarded as an inert cellular layer lining the blood vessels, but it has since been acknowledged as an important organ with autocrine and paracrine functions.