Cardiovascular disease is a leading cause of death and significant burden on our health system. As existing drug treatments remain less than ideal, we need additional effective strategies for management of these patients. Reducing nerve firing directed at the heart, which may exacerbate heart damage and cause sudden death, is crucial following heart attacks. A recently discovered hormone, urocortin 2 (Ucn2), has been proposed as novel therapeutic agent in cardiovascular disease. We have recently shown that Ucn2 dramatically reduces heart nerve excitation. We propose investigating the effects of this hormone as a novel therapeutic agent in an animal model of heart attack with particular emphasis on the heart nerve excitation. We will also determine whether Ucn2 inhibits adverse nerve activity in healthy humans and patients with heart failure. These studies should clarify the true therapeutic potential of Ucn2 in cardiovascular disease.