Abstract 12575: Cellular Basis of C-Type Natriuretic Peptide Produced Augmentation on Left Ventricular Systolic and Diastolic Functional Performance in Heart Failure

Background: In addition to its well-known vasodilating and natriuretic actions, C-type natriuretic peptide (CNP), has been viewed as an endogenous inhibitor of the renin-angiotensin system, but its direct cardiac effects remain controversial. In heart failure (HF), circulating and myocardial CNP levels are increased, which may alter LV functional response to CNP. However, the alterations and cellular mechanisms of CNP-induced cardiac response in HF remain unclearly defined. We assessed the hypothesis that in HF, CNP might produce enhanced positive modulation on myocyte [Ca2+]i transient ([Ca2+]iT) and L-type Ca2+ current (ICa,L) and improve LV and myocyte functional performance. Methods: We assessed LV systolic and diastolic function and compared myocyte contractile, [Ca2+]iT, and ICa,L responses to a clinically relevant dose of CNP (2 μg/kg bolus plus 0.4 μg/kg/min, iv, 10 min) in 12 normal (N) and 12 age-matched adult rats with isoproterenol (ISO)-induced HF (2 months after 170 mg/kg, sq, for 2 days). R...