The immediate effects of the hOrmone Urocortin on the nerve Control of blood pressure and Heart ratE.

Cardiovascular disease is a leading cause of death and significant burden on our health system. Existing drug treatments remain less than ideal. We need additional effective strategies for management of these patients. Reducing sympathetic nerve firing directed at the heart, which may exacerbate heart damage and cause sudden death, is desirable following heart attacks. A family of hormones, the urocortins (Ucn), have been proposed as novel therapeutic agents in this setting. We propose to determine whether Ucn can also inhibit sympathetic nerve activity (measured in the leg) in 8 healthy male volunteers and 8 males with stable heart failure. Participants will receive in a random order either Ucn2 (25 ug over 60 min) or matching placebo infusions on 2 separate occasions separated by 8 weeks. Each study day will occur on the fourth day of identical and constant salt controlled diets. On the morning of each study day, subjects will positioned in a lazy-boy reclined chair where they will remain for the duration of the study. Microneurography needles will be inserted in the right superficial peroneal nerve in the lower leg. Blood pressure will be measured continuously throughtout the infusion. Nerve activity recordings and blood sampling will occur at 5-15 minute intervals from 30 minutes prior to infusion for 2 hours These studies should clarify the true therapeutic potential of Ucn in cardiovascular disease.