Angiotensin II-induced increase in myocardial distensbility 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; Pimentel-Nunes P (Author) FMUP; Lima-Carneiro A (Author) Other; Fontes-Carvalho R (Author) FMUP; Soares JB (Author) Other; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: European Heart Journal

Initial page: 478

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): Angiotensin II (AngII) is a vasoactive peptide with central actions in the cardiovascular system. Besides its important positive inotropic effect, it was recently shown that it acutely decreases myocardial stiffness. Although endothelin-1 (ET-1) and the endocardial endothelium also modulate myocardial diastolic properties, their interaction with AngII at this level has not yet been investigated. Effects of increasing concentrations of AngII (10-9, 10-8, 10-7, 10-6, 10-5 M) were studied in rabbit right papillary muscles immersed in a modified Krebs solution (0.6Hz; 1.8mM Ca2+; 35°C) in the following conditions: (1) intact endocardial endothelium (Protocol A; n=11); (2) after selective removal of endothelial endocardium with Triton X-100 (0.5%; 1s; Protocol B; n=10); (3) with intact endocardial endothelium in presence of PD-145065, a nonselective endothelin receptor antagonist (Protocol C; 10-7 M; n=9); and (4) with intact endocardial endothelium 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), maximum velocity of tension rise and decline (dT/dtmax and dT/dtmin, respectively), muscle length and peak shortening (PS). Results presented as mean ± standard error (p<0.05). In Protocol A, Ang II induced a concentration dependent positive inotropic effect, increasing at 10-5 M 43.3±6.25% AT, 58.6±9.6% dT/dtmax, 49.2±9.8% dT/dtmin and 35.8±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 1.020±0.004 L/Lmax. Restoring muscle length to Lmax decreased 46.1±4.0% passive tension, indicating increased myocardial distensibility or decreased stiffness. When the endocardial endothelium was damaged (Protocol B) the maximal concentration of AngII only increased muscle length to 1.003±0.002 L/Lmax, which corresponded to a decrease of passive tension of just 13.9±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 concentrationdependent acute increase in myocardial distensibility. This effect is attenuated by the selective removal of the endocardial endothelium and completely abolished in the presence of the ET-1 receptor antagonists. 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: World Congress of Cardiology, published in journal, European Heart Journal. 2006; Vol.27(Suppl.1):478-478.