beta-adrenergic stimulation acutely increases myocardial distensibility - A PKA, PKC and Na+/H+ exchanger mediated effect.

• Type: Summary of Presentation in an International Conference
• Date: 2007

Authors

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

Conference proceedings International

Title: Journal of the American College of Cardiology

Pages: 408A-408A

56th Annual Scientific Session of the American-College-of-Cardiology.

New Orleans, 24 a 27 de Mar de 2007

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Background: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; 10-10-10-5M) were evaluated in isolated right papillary muscles from New-Zealand White-rabbits (Krebs-Ringer: 1,8mM CaCl2, 35ºC) 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-N-isobutil)-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. Conclusions:This study demonstrated that β-adrenergic stimulation increases myocardial distensibility, modulated by the activation of 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, where an hyperactivation and β-adrenoceptor desensitization is present.

Language: English

Type (Professor's evaluation): Scientific

Notes: 56th Annual Scientific Session, published in journal, Journal of the American College of Cardiology 2007; 49(Suppl. A): 408A.