Beta-adrenergic stimulation acutely increases myocardial distensibility: a novel PKA, PKC and Na+/H+ exchanger-mediated effect.

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

Authors

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

Conference proceedings International

Title: European Journal of Heart Failure

Initial page: 169

ESC Annual Congress 2006

Helsínquia, Finlândia, 17 a 20 de Junho de 2006

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

CORDIS: Health sciences > Medical sciences > Medicine > Cardiology

Other information

Resumo (PT): Background: Recent studies suggested that titin phosphorylation by PKA induces an increase of myocardial distensibility. As ~-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,SmM CaC12, 35°C) in the absence (n=9) or presence of: (i) PKA inhibitor, KT5720 (10- 6M; n=9); (it) PKC inhibitor, chelerythrine (CHE; 10-5M; n=9); or (iii) Na+/H + exchanger inhibitor, 5-(N-mefil-N-isobufil)-amiloride (MIA; 10- 6M; n=8). Reported parameters include: active tension (AT; mN/mm2), maximum velocities of tension rise and decline (dT/dtma,x and dT/dtmin, respectively; mN/mm2/s), passive tension (PT; mN/mm 2) and muscle length (L; L/LmaxQ. Only significant results (means4-SEM, p<0.05) are given, expressed as % change from baseline. Results: At baseline, ISO induced concentration-dependent positive inotropic and lusitropic effects ma, ximaJ at 10-5M, which increased 106.64-17.9% AT, 296.94-35.8% dT/dtma, x and 198.94-21.1% 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/Lma, x. Correcting muscle length to its initial value resulted in a 27.14-5.22% 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 ~-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 hyperacfivafion and ~-adrenoceptor desensitization.

Language: English

Type (Professor's evaluation): Scientific

Notes: ESC Annual Congress 2006, published in journal, European Journal of Heart Failure. 2006; Vol.5(Suppl.1):169-169.