Temple, Case Western scientists receive $3 million NIH grant to study pathway behind heart failure Like a bad water pump that fails to circulate coolant in a car engine, a failing heart struggles to pump blood through the body, causing symptoms of fatigue, shortness of breath, and swelling in the legs and feet. As heart failure progresses, the heart itself becomes increasingly unable to contract effectively, owing to changes in the molecules that control the heart, particularly a small gaseous molecule called nitric oxide. Nitric oxide is carried by red blood cells and acts as a signal to relax arteries and increase blood flow to heart tissue. It is also produced within heart cells, where it chemically combines with proteins in a process known as S-nitrosylation. More than 20,000 known S-nitrosylation events turn proteins "on" or "off," including proteins that make up the heart's beta-adrenergic receptor (βAR) system - the system that regulates the "fight-or-flight" response that allows physical activity. In heart failure, both S-nitrosylation and βAR activity are altered, with significant impacts on cardiac function.