Abstract 4394: Chronic Administration of Urocortin 2 Prevents the Development of Heart Failure in an Animal Model of Hypertensive Heart Disease
Background: Recently, novel corticotropin-releasing factor (CRF)-related peptides named Urocortin (Ucn) 1, 2, and 3 were described. Available data suggest that the Ucns are part of a peripheral CRF system modulating cardiovascular function and mediating cardiovascular responses to stress. Chronic Ucn2 administration induced sustained blood pressure lowering and prevented the development of left ventricular hypertrophy (LVH) in an animal model of hypertensive heart disease. However, no data are available whether chronic administration of Ucn2 may prevent the progression from LVH to heart failure.
Methods: Experiments were performed in Dahl salt-sensitive rats. Animals were fed a high salt diet containing 4% NaCl to induce arterial hypertension, LVH, and heart failure. From the phase of LVH on (after 7 weeks of high salt diet), animals were injected with either Ucn2 at a dose of 2.5 μg/kg body weight or vehicle b.i.d. Animals underwent repetitive tail cuff blood pressure measurements and echocardiographic analysis of LV dimension and function at baseline (prior to first injection of Ucn2) and after 5 weeks of b.i.d. treatment with Ucn2.
Results: Results are given in the following table⇓ as mean (± SD). No differences in heart weight/body weight ratios between Ucn2- and vehicle treated animals were found after 5 weeks of treatment.
Conclusion: Chronic CRF receptor stimulation by Ucn2 in the severely hypertensive Dahl salt-sensitive rat, an animal model of hypertensive heart disease, prevents the progression from LVH to LV dilatation and the deterioration of LV function. Thus, chronic administration of Ucn2 might represent a novel approach to the prevention of heart failure.