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Since its discovery by Furchgott and Zawadzki in 1980,1 endothelium-derived relaxing factor (EDRF) has been shown to play a central role in the cardiovascular system.2 This endothelial product is chemically equivalent to nitric oxide (NO)3'4 or a biochemical congener thereof,5 and relaxes vascular smooth muscle in association with activating guanylyl cyclase and increasing cGMP. Operating through this basic paradigm, EDRF/NO is a critical determinant of several normal physiological responses of the vascular system that are essential for the maintenance of tissue perfusion.6,7 In this issue and the forthcoming December issue of Circulation, the potential role of EDRF/NO in two related vascular responses is examined. Tagawa and

Ischemia, hyperemia, exercise, and nitric oxide. Complex physiology and complex molecular adaptations.