Resumo (PT):
Background: The urocortin (Ucn) peptides Ucn1, Ucn2, and Ucn3 are
recently isolated members of the corticotropin-releasing factor (CRF)
family. Urocortin II enhances contractility via CRF2 receptor-mediated
stimulation of protein kinase A. As protein kinase A is a well known
modulator of diastolic function, in the current study, we investigated the,
yet unknown, acute effects of Ucn2 on the diastolic properties of the
myocardium.
Methods: Effects of increasing concentrations of Ucn2 (10-8 to 10-6M)
were evaluated in isolated right papillary muscles (n=12) from male New
Zealand White rabbits (Krebs-Ringer: 1,8mM CaCl2, 35°C). 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 (mean±SEM, p<0.05) are given,
expressed as % change from baseline.
Results: Ucn2 increased 68.4±7.5% AT, 187.5±13.5% dT/dtmax and 140.3±13.8% dT/dtmin in the concentration range of this study. It also
promoted a concentration-dependent increase in resting muscle length
up to 1.012±0.004 L/Lmax at the highest concentration. Correcting muscle
length to its initial value resulted in a 29.6±8.9% decrease of PT,
indicating a decrease in muscle stiffness.
Conclusion: The present study demonstrated a novel effect of Ucn2 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 30% lower filling pressures.
These results support a role for Ucn2 in the pathophysiology of heart
failure and points out to its therapeutic potential in this disease.
Language:
English
Type (Professor's evaluation):
Scientific
Notes:
Heart Failure 2007, published in journal, European Journal of Heart Failure Supplements 2007; 6 (Suppl 1): 39-40.