The acute increase in myocardial distensibility induced by beta-adrenergic stimulation is mediated by PKA, PKC and Na+/H+ exchanger.

• Type: Summary of Presentation in an International Conference
• Date: 2006

Authors

Falcão-Pires I (Author) FMUP; Fontes-Sousa P (Author) Other; Brás-Silva C (Author) FMUP; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: European Heart Journal

Initial page: 846

World Congress of Cardiology

Barcelona, SPAIN, 02 a 06 de Setembro de 2006

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Purpose: Recent studies suggested that titin phosphorylation by PKA induces an increase of myocardial distensibility. As β-adrenergic stimulation is one of the most important stimuli for PKA activation, the present study investigated its effects on myocardial distensibility, as well as some of the underlying mechanisms. Methods: Effects of increasing concentrations of isoproterenol (ISO; 10-10 to 10- 5M) were evaluated in isolated right papillary muscles from male New Zealand White rabbits (Krebs-Ringer: 1,8mM CaCl2, 35°C) in the absence (n=9) or presence of: (i) PKA inhibitor, KT5720 (10-6M; n=9); (ii) PKC inhibitor, chelerythrine (CHE; 10-5M; n=9); or (iii) Na+/H+ exchanger inhibitor, 5-(N-metil-Nisobutil)- amiloride (MIA; 10-6M; n=8). Reported parameters include: active tension (AT; mN/mm2), maximum velocities of tension rise and decline (dT/dtmax and 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: At baseline, ISO induced concentration-dependent positive inotropic and lusitropic effects maximal at 10-5M, which increased 106.6±17.9% AT, 296.9±35.8% dT/dtmax and 198.9±21.1% dT/dtmin. These effects were not significantly affected by any of the inhibitors used in this study. Concerning myocardial distensibility, increasing concentrations of ISO progressively increased resting muscle length up to 1.03 L/Lmax. Correcting muscle length to its initial value resulted in a 27.1±5.22% decrease of RT, indicating decreased stiffness or an increase of myocardial distensibility. This effect was almost abolished by the inhibition of PKA, PKC or Na+/H+ exchanger. Conclusion: The present study demonstrated that β-adrenergic stimulation promotes an increase of myocardial distensibility, modulated by the activation of several intracellular pathways, including PKA, PKC and Na+/H+ exchanger. This effect represents a novel mechanism of modulation of the diastolic properties of the myocardium by the sympathetic nervous system. This might have pathophysiologic implications in heart failure, as this syndrome is characterized by sympathetic hyperactivation and β-adrenoceptor desensitization.

Language: English

Type (Professor's evaluation): Scientific

Notes: XVth World Congress of Cardiology, published in journal, European Heart Journal. 2006; Vol.27(Suppl.1): 846-846.