Abstract 1624: Urotensin II: A Novel Neurohumoral Modulator of Diastolic Function
Background: Urotensin II (U-II) is a peptide expressed, together with its receptor, in the central nervous system and in many peripheral tissues, including the cardiovascular system. In the latter, U-II has been shown to modulate the vascular tonus, myocardial contraction, heart rate and cardiac fibrosis and hypertrophy. In the current study, we investigated the, yet unknown, acute effects of U-II on the diastolic properties of the myocardium.
Methods: The effects of increasing concentrations of U-II (10−8 to 10−6M) were evaluated in isolated right papillary muscles, from male New Zealand rabbits (Krebs-Ringer: 1.8mM CaCl2, 35°C), with intact (n=16) and damaged endocardial endothelium (EE; Triton X-100; 0.5%; n=9). 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 (means±SEM, p<0.05) are given, expressed as % change from baseline.
Results: U-II had no significant effects on AT and dT/dtmax in the concentration range of this study. However, with regard to the diastolic properties of the myocardium, in addition to increasing dT/dtmin, U-II promoted a concentration-dependent increase in resting muscle length up to 1.006±0.0013 L/Lmax at the highest concentration. Correcting muscle length to its initial value resulted in a 19.2±9.63% decrease of PT, indicating decreased muscle stiffness. These effects were not altered significantly when EE was damaged.
Conclusion: The present study demonstrated a novel effect of U-II 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 20% lower filling pressures. Furthermore, as the plasmatic levels of U-II are increased in heart failure, these results might help to better understand the pathophysiology of this syndrome.