Resumo (PT):
As recently described, angiotensin II (AngII) acutely increases myocardial distensibility.
Although endothelin-1 (ET-1) and the endocardial 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 (10-8, 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+; 35ºC) in the following conditions: (1) with intact EE (Protocol A; n=11); (2) after
selective removal of EE with Triton X-100 (0.5%; Protocol B; n=8); and (3) with intact EE
in presence of PD-145065, a nonselective endothelin receptor antagonist (Protocol C; 10-
7M; n=8), or BQ-123 (Protocol D; 10-7M; n=8), a selective ET-A receptor antagonist, or NGnitro-
L-arginine, an inhibitor of nitric oxide synthesis (Protocol E; 10-5M; n=8). Calculated
parameters: active tension (AT), maximum velocity of tension rise (dT/dtmax), passive
tension and muscle length. Results presented as mean±SE (p<0.05).
In Protocol A, Ang II induced a concentration dependent positive inotropic effect, increasing
at 10-5M 43.3±6.3% AT and 58.6±9.6% dT/dtmax. With regard to the diastolic properties,
the same concentration of AngII induced an 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 an increase in myocardial distensibility. When the EE was damaged
(Protocol B) this effect was abolished. In Protocols C, D and E the effects of AngII 10-5 M
were only attenuated inducing an increase in passive muscle length which corresponded to
a decrease in passive tension of 24.5±3.6%, 16.1±6.0% and 19.3±6.2%, respectively.
In conclusion, Ang II induces a concentration-dependent acute increase in myocardial
distensibility. This effect is abolished by the selective removal of EE and attenuated in the
presence of the ET-1 receptor antagonists and an inhibitor of nitric oxide synthesis. The
interaction between AngII, ET-1 and the EE in the modulation of the diastolic myocardial
properties is a novel
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): 53A-53A.