Stretch-induced compliance: a novel adaptive biological mechanism following acute cardiac load

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Leite Moreira, AM (Autor) FMUP; Almeida Coelho, J (Autor) Outra; Neves, JS (Autor) FMUP; Pires, AL (Autor) Outra; Ferreira-Martins J (Autor) FMUP; Castro Ferreira, R (Autor) FMUP; Ladeiras-Lopes R (Autor) FMUP; Conceicao, G (Autor) Outra; Miranda Silva, D (Autor) FMUP; Rodrigues, P (Autor) Outra; Hamdani, N (Autor) Outra; Herwig, M (Autor) Outra; Falcao Pires, I (Autor) FMUP; Paulus, WJ (Autor) Outra; Linke, WA (Autor) Outra; Andre P Lourenco (Autor) FMUP; Leite-Moreira AF (Autor) FMUP

Revista

Título: Cardiovascular Research

Vol. 114

Páginas: 656-667

ISSN: 0008-6363

Editora: Oxford University Press

Indexação

ISI Web of Knowledge - 17 Citações

Scopus - 20 Citações

Outras Informações

ID Authenticus: P-00N-TBY

DOI: 10.1093/cvr/cvy026

Abstract (EN): Aims The heart is constantly challenged with acute bouts of stretching or overload. Systolic adaptations to these challenges are known but adaptations in diastolic stiffness remain unknown. We evaluated adaptations in myocardial stiffness due to acute stretching and characterized the underlying mechanisms. Methods and results Left ventricles (LVs) of intact rat hearts, rabbit papillary muscles and myocardial strips from cardiac surgery patients were stretched. After stretching, there was a sustained >40% decrease in end-diastolic pressure (EDP) or passive tension (PT) for 15 min in all species and experimental preparations. Stretching by volume loading in volunteers and cardiac surgery patients resulted in E/E' and EDP decreases, respectively, after sustained stretching. Stretched samples had increased myocardial cGMP levels, increased phosphorylated vasodilator-stimulated phosphoprotein phosphorylation, as well as, increased titin phosphorylation, which was reduced by prior protein kinase G (PKG) inhibition (PKGi). Skinned cardiomyocytes from stretched and non-stretched myocardia were studied. Skinned cardiomyocytes from stretched hearts showed decreased PT, which was abrogated by protein phosphatase incubation; whereas those from non-stretched hearts decreased PT after PKG incubation. Pharmacological studies assessed the role of nitric oxide (NO) and natriuretic peptides (NPs). PT decay after stretching was significantly reduced by combined NP antagonism, NO synthase inhibition and NO scavenging, or by PKGi. Response to stretching was remarkably reduced in a rat model of LV hypertrophy, which also failed to increase titin phosphorylation. Conclusions We describe and translate to human physiology a novel adaptive mechanism, partly mediated by titin phosphorylation through cGMP-PKG signalling, whereby myocardial compliance increases in response to acute stretching. This mechanism may not function in the hypertrophic heart.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12