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Urocortin 2 acute effects on the diastolic properties of the
myocardium
M. Gomes 1,2 , S. Silva 1,2 , P. Ferreira 1,2 , P. Fontes-Sousa 3 , A. Leite-Moreira 1 and C. Brás-
Silva 1,4
1 Department of Physiology, Faculty of Medicine, University of Porto, Portugal.
2 Faculty of Sciences, University of Porto, Portugal.
3 Laboratory of Pharmacology and Neurobiology-UMIB, Institute of Biomedical Sciences Abel Salazar,
University of Porto (ICBAS-UP), Porto, Portugal.
4 Faculty of Nutrition and Food Sciences, University of Porto, Portugal.
The urocortin (Ucn) peptides are recent isolated members of the highly conserved
corticotrophin-releasing factor (CRF) family [1-2]. Ucn2 enhances contractility via CRF2
receptor-mediated stimulation of protein kinase (PK) A. As PKA is a well known modulator of
diastolic function, we investigated the acute effects of Ucn2 on myocardial diastolic properties.
The effects of increasing concentrations of Ucn2 (10 -10 to 10 -6 M) were evaluated in right
ventricular papillary muscles isolated from male New Zealand White rabbits (Krebs-Ringer:
1,8mM CaCl2, 35°C), in the presence (n=12) and in the absence of: (i) PKA inhibitor (H89, 10 -
6 M, n=9) or (ii) PKC inhibitor (Chelerythrine, 10 -5 M, n=9). Reported parameters include
passive tension (PT; mN/mm2) and muscle length (L; L/Lmax).
Ucn2 induced a concentration-dependent increase in resting muscle length up to 1.012±0.004
L/Lmax at 10 -6 M. Correcting muscle length to its initial value resulted in a 29.6±8.9% decrease
of PT, indicating a decrease in muscle stiffness. This effect was attenuated in the presence of
either PKA or PKC inhibitor. Ucn2 (10 -6 M) induced an increase in resting muscle length of
1.005±0.002 L/Lmax, in the presence of H89, and of 1.006±0.002 L/Lmax in the presence of
Chelerythrine, corresponding to a decrease of PT of only 11.0±4.0%, and 13.3±6.4%,
respectively.
Ucn2 acutely decreases myocardial stiffness, an effect dependent on PKA and PKC activation.
This 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 findings reinforce the
relevance of Ucn2 in the pathophysiology of heart diseases and also its potential clinical
importance.
References:
[1] Vaughan, J.; Donaldson, C.; Bittencourt, J.; Perrin, M.; Lewis, K.; Sutton, S.; Chan, R.; Turnbull,
A.; Lovejoy, D.; Rivier, C.; Rivier, J.; Sawchenko, P.; Vale, W.; Urocortin, a mammalian neuropeptide
related to fish urotensin I and corticotrophin-releasing factor; Nature 1995; 378: 287-292.
[2] Davidson SM, Rybka AE, Townsend PA: The powerful cardioprotective effects of urocortin and the
corticotropin releasing hormone (CRH) family. Biochem Pharmacol, 2008, 77, 141–150.
36 3 rd meeting of young researchers at UP