Disturbed myocardial response to endothelin-1 and angiotensin II in heart failure.

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

Authors

Brás-Silva C (Author) FMUP; Castro-Chaves P (Author) FMUP; Monteiro-Sousa D (Author) Other; Duarte A (Author) Other; Nunes P (Author) Other; Fontes-Sousa A (Author) Other; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: Circulation

Initial page: 1600

79th Scientific Sessions of the American Heart Association

Chicago, IL, EUA, 12 a 15 de Novembro 2006

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): In the present study, we investigated the myocardial effects of Endothelin-1 (ET-1) and Angiotensin II (AngII), with a special emphasis on diastolic function, in normal and failing hearts, as well as, their modulation by the endocardial endothelium (EE). New Zealand white rabbits were treated with Doxorubicin (2mg/kg, iv/ 8 weeks, Heart Failure-HF Group) or saline (Control Group). The contractile effects of increasing concentrations of ET-1, Sarafotoxin S6c (SRTXc, selective ETB receptor agonist, non-specific ETB1/ETB2), IRL1620 (selective endothelial ETB1 receptor agonist), and AngII were studied in papillary muscles (n=101, Krebs-Ringer: 1.8mM CaCl2, 35°C) from the: (i) Control Group with intact EE; (ii) Control Group with damaged EE and (iii) HF Group. In the Control Group with intact EE, ET-1 and Ang II promoted dose-dependent positive inotropy. This effect was maintained in the absence of EE and in the HF Group in the case of ET-1, but was attenuated in these groups in response to AngII. Both ET-1 and AngII increased myocardial distensibility when in the presence of intact EE. This effect was blunted in failing muscles and in muscles with damaged EE. Selective ETB stimulation with SRTXc did not significantly alter myocardial function in the Control Group with intact EE, but induced a positive inotropic effect in the presence of a damaged EE or HF. In contrast, selective endothelial ETB1 stimulation with IRL1620 induced a dose dependent negative inotropic effect in the Control Group with intact EE, effect that was abolished after damaging EE and reduced in the HF Group. This study showed that ET-1 and AngII promote, in addition to the well known effects on systolic function, an increase in diastolic distensibility, which is dependent on the EE functional integrity and that is almost absent in the failing myocardium. The response pattern to ETB receptors stimulation in the HF Group suggests the presence of a dysfunctional EE. These results reinforce the importance of endothelial ETB1 receptors as markers of endothelial function and provide new elements for the comprehension of the pathophysiology of HF.

Language: English

Type (Professor's evaluation): Scientific

Notes: 79th Scientific Sessions of the American Heart Association, published in journal, Circulation.2006; 114: 1600.