Only 30% of the overall cardiovascular benefit of angiotensin-converting enzyme (ACE) inhibitors is due to their hypotensive effect, mostly by restoring endothelial function. ACE inhibitors prevent degradation of the potent vasodilator bradykinin and inactivation of vasculoprotective nitric oxide (NO). Bradykinin itself stimulates the release of NO and endothelium-derived hyperpolarizing factor (EDHF), an as yet unidentified vasorelaxant factor that comediates with NO the hypotensive and vascular effects of the ACE inhibitors. EDHF rather than NO is thought responsible for bradykinin- induced vasodilation of human resistance vessels via hyperpolarization of the vessel wall. Elucidating the relative contributions of NO and EDHF to vasorelaxation in large and small coronary arteries is the key to understanding—and optimizing—the cardiovascular protective effects of the ACE inhibitors...