Neuroendocrine systems are central to key heart disease processes such as cardiovascular remodeling, fibrosis, apoptosis, paradoxical coronary constriction, and salt-andwater retention. The neuroendocrine response to severe ischemia leads to increased arterial pressure and afterload, and compounds myocardial oxygen debt. Acute ACE inhibition in pacing-induced ischemia modulates vasoconstrictor hormone secretion, while chronic ACE inhibition appears to improve myocardial ischemia via long-term neurohormone- mediated structural effects. Thus, inhibition of angiotensin II formation itself inhibits the sympathetic system, and possibly also aldosterone and endothelin secretion. Crucially, it also reduces the breakdown of bradykinin. Long-term improvement in coronary structure and endothelial function during chronic ACE inhibition normalizes the paradoxical vascular response to neuroendocrine stimuli...