Abstract 3826: Effects of Longer-Term Administration of Urocortin 2 on Left Ventricular Function and Survival in Rats With Severe Heart Failure
Background: Recent experimental data demonstrate that urocortin 2 (Ucn2), a member of the corticotropin-releasing factor (CRF)-related peptide family, induces when administered acutely potent beneficial hemodynamic effects via CRF receptor 2 stimulation in animal models of heart failure (CHF) and patients with CHF. In an animal model of hypertensive heart disease, chronic administration of Ucn2 lowered blood pressure and prevented the development of left ventricular (LV) hypertrophy and failure. However, no data are available on the effects of chronic administration of Ucn2 on LV function and survival in established CHF.
Methods: Experiments were performed in Dahl salt-sensitive rats. Animals were fed a high salt diet (HSD) containing 4% NaCl to induce arterial hypertension, LV hypertrophy, LV dysfunction, and CHF. From the phase of LV dysfunction on (after 12 weeks of HSD), animals were injected with either Ucn2 at a dose of 2.5 μg/kg body weight or vehicle i.p. b.i.d. Animals underwent tail cuff blood pressure measurements and echocardiographic analysis of LV dimension and function at baseline (prior to first injection of Ucn2) and after 4 weeks of b.i.d. treatment with Ucn2.
Results: Results are given in the following table⇓ as mean±SD.
Conclusion: One month of daily CRF receptor 2 stimulation by Ucn2 in Dahl salt-sensitive rats with severe heart failure significantly improves LV function, partially reverts structural LV abnormalities, and appears, on early followup, to beneficially affect survival. Data from this study suggest that longer-term administration of Ucn2 might represent a novel, safe, and beneficial approach to the treatment of heart failure.