Abstract 1241: Urocortin 2 Acutely Increases Diastolic Distensibility
The urocortin (Ucn) peptides Ucn1, Ucn2, and Ucn3 are recently isolated members of the corticotropin-releasing factor (CRF) family. Ucn2 enhances contractility via CRF2 receptor-mediated stimulation of protein kinase A. As protein kinase A is a well known modulator of diastolic function, in the current study, we investigated the, yet unknown, acute effects of Ucn2 on the diastolic properties of the myocardium. Effects of increasing concentrations of Ucn2 (10 – 8 to 10 – 6M) were evaluated in isolated right papillary muscles (n=12) from male New Zealand White rabbits (Krebs-Ringer: 1,8mM CaCl2, 35°C). Reported parameters include: active tension (AT; mN/mm2), maximum velocities of tension rise and tension decline (dT/dtmax e dT/dtmin, respectively; mN/mm2/s), passive tension (PT; mN/mm2) and muscle length (L; L/Lmax). Only significant results (mean±SEM, p<0.05) are given, expressed as % change from baseline. Ucn2 promoted concentration-dependent positive inotropic and lusitropic effects (it increased 68.4±7.5% AT, 187.5±13.5% dT/dtmax and 140.3±13.8% dT/dtmin at 10−6). It also promoted a concentration-dependent increase in resting muscle length up to 1.012±0.004 L/Lmax at the highest concentration. Correcting muscle length to its initial value resulted in a 29.6±8.9% decrease of PT, indicating a decrease in muscle stiffness. The present study demonstrated a novel effect of Ucn2 on the diastolic properties of the myocardium, which consisted on a concentration dependent acute decrease of myocardial stiffness. This effect is a potentially powerful physiologic mechanism, as it may allow the heart to reach the same diastolic volume with up to 30% lower filling pressures.
These results support a role for Ucn2 in the pathophysiology of heart failure and points out to its therapeutic potential in this disease.