Abstract 5956: Modulation of Urocortin 2 Contractile EFFects by Endocardial Endothelium
Purpose: The urocortin (Ucn) peptides Ucn1, Ucn2, and Ucn3 are recently isolated members of the corticotropin-releasing factor family. Ucn2 promotes positive inotropic and lusitropic effects and both endothelium-dependent and -independent vasodilatation. In the current study, we investigated the modulation of Ucn2 contractile effects by endocardial endothelium (EE).
Methods: The effects of increasing concentrations of Ucn2 (10 –10 to 10 – 6M) were evaluated in isolated right papillary muscles (Krebs-Ringer: 1.8mM CaCl2, 35°C) with intact EE (n=11) and after damaging EE (0.5% Triton X-100, n=12). Reported parameters include: active tension (AT; mN/mm2) and maximum velocities of tension rise and tension decline (dT/dtmax and dT/dtmin, respectively; mN/mm2/s). Only significant results (mean±SEM, p<0.05) are given, expressed as % change from baseline.
Results: Ucn2 induced concentration-dependent positive inotropic and lusitropic effects in muscles with intact EE (at 10 – 6M it increased 65.6±5.2% AT, 196.9±16.7 dT/dtmax and 145.0±13.5% dT/dtmin). These effects were potentiated in papillary muscles with damaged EE. In this condition, the higher concentration of Ucn2 increased 169.1±39.2% AT, 412.5±43.9% dT/dtmax and 296.7±56.7%dT/dtmin.
Conclusions: This study shows that the positive inotropic and lusitropic effects induced by Ucn2 are enhanced in the presence of endocardial endothelial dysfunction. These findings reinforce the importance of Ucn2 in the regulation of myocardial function and provide new elements for the comprehension of the pathophysiology of HF, a condition where Ucn2 levels are increased and endothelial dysfunction might be present.