Angiotensin II-induced increase in myocardial distensibility is modulated by the endocardial endothelium and endothelin-1.

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

Authors

Castro-Chaves P (Author) FMUP; Lima-Carneiro A (Author) Other; Pimentel-Nunes P (Author) FMUP; Fontes-Carvalho R (Author) FMUP; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: European Journal of Heart Failure

Pages: 73-74

ESC Annual Congress 2006

Helsínquia, Finlândia, 17 a 20 de Junho de 2006

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Angiotensin II (AngII) is a vasoacfive pepfide with central actions in the cardiovascular system. Besides its important positive inotropic effect, it was recently shown that it acutely decreases myocardial stiffness. A1-though endothelin I(ET-1) and the endocardiaJ endothelium (EE) also modulate myocardial diastolic properties, their interaction with AngII at this level has not yet been investigated. The effects of increasing concentrations of AngII (10-9, 10-8, 10-7, 10- 6, 10-5 M) were studied in rabbit right ventricular papillary muscles immersed in a modified Krebs solution (0.6Hz; 1.8mM Ca2+; 35°C) in the following conditions: (1) intact EE (Protocol A; n=ll); (2) after selective removal of EE with Triton X-100 (0.5%; ls; Protocol B; n=10); (3) with intact EE in presence of PD-145065, a nonselective endothelin receptor antagonist (Protocol C; 10-7 M; n=9); and (4) with intact EE in presence of BQ- 123 (Protocol D; 10-7 M; n=7), a selective ET-A receptor antagonist. Calculated parameters: passive tension, active tension (AT), ma, ximum velocity of tension rise and decline (dT/dtma, x and dT/dtmin, respectively), muscle length and peak shortening (PS). Results presented as mean 4- standard error (p<0.05). In Protocol A, Ang II induced a concentration dependent positive inotropic effect, increasing at 10-5 M 43.34-6.25% AT, 58.64-9.6% dT/dtma,x , 49.24-9.8% dT/dtmin and 35.84-4.4% PS. This effect was attenuated in protocols B, C and D. With regard to the diastolic properties, AngII induced a concentration dependent increase in passive muscle length up to 1.0204-0.004 L/Lmax. Restoring muscle length to Lma, x decreased 46.14-4.0% passive tension, indicating increased myocardial distensibility or decreased stiffness. When the EE was damaged (Protocol B) the ma,x imaJ concentration of AngII only increased muscle length to 1.0034-0.002 L/Lma, x, which corresponded to a decrease of passive tension of just 13.94-4.5%. In Protocols C and D the effects of AngII on passive muscle length and tension were abolished. In conclusion, Ang II induces a concentration-dependent acute increase in myocardial distensibility. This effect is attenuated by the selective removal of the endocardiaJ endothelium and completely abolished in the presence of the ET-1 receptor antagonists (BQ-123 and PD-145065). The interaction between AngII, ET-1 and the endocardial endothelium in the modulation of the diastolic myocardial properties is a novel finding with potential pathophysiologic and therapeutic implications in heart failure, that deserves further investigation.

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):73-74.