Effects of adrenomedullin on systolic and diastolic myocardial function

• Tipo: Artigo em Revista Científica Internacional
• Data: 2009

Autores

Ana Patricia Fontes Sousa (Autor) ICBAS; Ana Luisa Pires (Autor) Outra; Catarina Santos Carneiro (Autor) Outra; Carmen Bras Silva (Autor) FMUP; Adelino F Leite Moreira (Autor) FMUP

Revista

Título: Peptides

Vol. 30 Nº 4

Páginas: 796-802

ISSN: 0196-9781

Editora: Elsevier

Indexação

ISI Web of Knowledge - 9 Citações

ISI Web of Science

Scopus - 9 Citações

Pubmed / Medline

Classificação Científica

CORDIS: Ciências da Saúde

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-003-MA2

DOI: 10.1016/j.peptides.2008.12.011

Resumo (PT): Adrenomedullin (AM) effects were studied in rabbit papillary muscles by adding increasing concentrations (10(-10) to 10(-6)M) either alone or after pre-treatment with l-NNA, indomethacin, AM22-52 (AM receptor antagonist), CGRP(8-37) (CGRP receptors antagonist), KT5720 (PKA inhibitor), as well as after endocardial endothelium (EE) removal. Passive length-tension relations were constructed before and after a single concentration of AM (10(-6)M). AM concentration-dependently induced negative inotropic and lusitropic effects, and increased resting muscle length (RL). At 10(-6)M, AT, dT/dt(max) and dT/dt(min) decreased 20.9+/-4.9%, 18.3+/-7.3% and 16.7+/-7.8%, respectively, and RL increased to 1.010+/-0.004L/L(max). Correcting RL to its initial value resulted in a 26.6+/-6.4% decrease of resting tension, indicating decreased muscle stiffness, also patent in the down and rightward shift of the passive length-tension relation. The negative inotropic effect of AM was dependent on its receptor, CGRP receptor, PKA, the EE and NO, while the effects of AM on myocardial stiffness were abolished by EE damage and NO inhibition. This latter effect represents a novel mechanism of acute neurohumoral modulation of diastolic function, suggesting that AM is an important regulator of cardiac filling.

Abstract (EN): Adrenomedullin (AM) effects were studied in rabbit papillary muscles by adding increasing concentrations (10(-10) to 10(-6) M) either alone or after pre-treatment with L-NNA, indomethacin, AM22-52 (AM receptor antagonist), CGRP(8-37) (CGRP receptors antagonist), KT5720 (PKA inhibitor), as well as after endocardial endothelium (EE) removal. Passive length-tension relations were constructed before and after a single concentration of AM (10(-6) M). AM concentration-dependently induced negative inotropic and lusitropic effects, and increased resting muscle length (RL). At 10(-6) M, AT, dT/dt(max) and dT/dt(min) decreased 20.9 +/- 4.9%,18.3 +/- 7.3% and 16.7 +/- 7.8%, respectively, and RL increased to 1.010 +/- 0.004 L/L(max). Correcting RL to its initial value resulted in a 26.6 +/- 6.4% decrease of resting tension, indicating decreased muscle stiffness, also patent in the down and rightward shift of the passive length-tension relation. The negative inotropic effect of AM was dependent on its receptor, CGRP receptor, PKA, the EE and NO, while the effects of AM on myocardial stiffness were abolished by EE damage and NO inhibition. This latter effect represents a novel mechanism of acute neurohumoral modulation of diastolic function, suggesting that AM is an important regulator of cardiac filling.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7