Abstract 3830: Chronic Administration of Urocortin 2 in Hypertension-Induced Hypertrophy: Effects on Intracellular Calcium Handling and Hemodynamics
Background: Urocortin 2 (Ucn2) is part of a peripheral corticotropin-releasing factor system. Vasodilatory, inotropic, and chronotropic effects in the heart and cardiovascular system of cardiomyopathic mice and improved intracellular calcium handling in isolated myocytes have been demonstrated after acute administration of Ucn2. Chronic Ucn2 administration induced sustained blood pressure lowering and prevented the development of left ventricular hypertrophy (LVH) and congestive heart failure (CHF) in an animal model of hypertensive heart disease. However, no data are available on the effects of chronic Ucn2 administration on intracellular calcium handling and hemodynamics during the development of CHF.
Methods: Experiments were performed in Dahl salt-sensitive rats. Animals were fed a high salt diet (containing 4% NaCl, HSD) to induce arterial hypertension, LVH, and CHF. From week 7 of HSD (phase of LVH) on, animals were injected with either Ucn2 (2.5 μg/kg body weight) or vehicle b.i.d. After 5 weeks of treatment the animals underwent tail cuff blood pressure measurements and echocardiographic analysis of LV dimension and function. To further quantify the cardiac effects of chronic Ucn2 administration, intracellular calcium cycling using Indo-1 together with hemodynamic parameters were analysed in isolated perfused rat hearts at the trough point 12 hours after the last administration of Ucn2.
Results: Results are given in the following as mean±SD:
Conclusion: Chronic application of Ucn2 in an animal model of hypertensive heart disease at the stage of LVH appears to preserve intracellular calcium handling and LV function, and prevents the development of CHF. Our results suggest preserved calcium sensitivity of myocardial contractile proteins in Ucn2-treated animals pointing to beneficial cardiac effects of Ucn2 beyond improved LV contractility.