Functional evidence for the existence of ETA-ETB receptor crosstalk in the heart.

• Tipo: Resumo de Comunicação em Conferência Internacional
• Data: 2007

Autores

Brás-Silva C (Autor) FMUP; Monteiro-Sousa D (Autor) Outra; Duarte AJ (Autor) Outra; Leite-Moreira AF (Autor) FMUP

Ata de Conferência Internacional

Título: European Journal of Heart Failure

Páginas: 145-146

Heart Failure 2007

Hamburgo, Alemanha, 09 a 12 de Junho de 2007

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

Resumo (PT): Endothelin (ET)-1 acts on ETA and ETB receptors. While the former increase inotropy, the latter can be subdivided in endothelial ETB1, which decrease inotropy, and myocardial ETB2, which increase inotropy. This study investigated, in rabbit papillary muscles, functional evidences of the existence of ETA-ETB receptor crosstalk in the heart. ET-1 (0.1- 10nM) was given in the presence of: (i) intact endocardial endothelium (EE, n=9); (ii) damaged EE (n=8); (iii) intact EE and BQ-123 (ETA antagonist, n=8); (iv) intact EE and BQ-788 (ETB2 antagonist, n=8); (v) intact EE and both BQ-788 and RES-701-1 (ETB1 antagonist, n=8); (vi) damaged EE and BQ-123 (n=8); (vii) damaged EE and BQ-788 (n=7). The effects of Sarafotoxin S6c (ETB agonist, 0.1nM-1μM) were evaluated in muscles with: (i) intact EE and in the presence (n=8) and in the absence (n=7) of BQ-123 and (ii) damaged EE and in the presence (n=9) and in the absence (n=7) of BQ-123.ET-1 alone elicited positive inotropic effects that were potentiated by concomitant inhibition of endothelial and myocardial ETB receptors. In muscles with damaged EE, ET-1 increased inotropy when ETA receptors were blocked, indicating that ETB2 receptors elicited a positive inotropic effect which could not be observed when EE was intact and ETB1 functional. Additionally, the negative inotropic effect induced by selective ETB activation was enhanced by ETA antagonism in the presence of an intact EE. On the other hand, the positive inotropic effect elicited by ETB stimulation in the absence of EE required the presence of active ETA. These results reveal that ET-1 activity is likely to depend on a complex balance of ETA- and ETB-mediated effects with factors such as functional endothelial integrity and efficiency of receptor subtype or receptor-effector coupling determining the overall response. These findings might help to improve our understanding about the role of ET-1 in the intrinsic modulation of cardiac function, and should be taken into account in the therapeutic studies using selective ETA or mixed ETA/ETB receptor antagonists.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Notas: Heart Failure 2007, published in journal, European Journal of Heart Failure. 2007; 6(Suppl.1):145-146.