Revisiting the slow force response: The role of the PKG signaling pathway in the normal and the ischemic heart

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Castro Ferreira, R (Author) FMUP; Neves, JS (Author) FMUP; Ladeiras-Lopes R (Author) FMUP; Leite Moreira, AM (Author) FMUP; Neiva Sousa, M (Author) Other; Almeida Coelho, J (Author) Other; Ferreira-Martins J (Author) FMUP; Leite-Moreira AF (Author) FMUP

Journal

Title: Revista Portuguesa de Cardiologia

Vol. 33

Pages: 493-499

ISSN: 0870-2551

Publisher: Sociedade Portuguesa De Cardiologia

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 10 Citations

Other information

Authenticus ID: P-009-X10

DOI: 10.1016/j.repc.2014.03.006

Abstract (EN): Introduction: The myocardial response to acute stretch consists of a two-phase increase in contractility: an acute increase by the Frank-Starling mechanism and a gradual and time-dependent increase in force generated known as the slow force response (SFR). The SFR is actively modulated by different signaling pathways, but the role of protein kinase G (PKG) signaling is unknown. In this study we aim to characterize the role of the PKG signaling pathway in the SFR under normal and ischemic conditions. Methods: Rabbit papillary muscles were stretched from 92 to 100% of maximum length (L-max) under basal conditions, in the absence (1) or presence of: a PKG agonist (2) and a PKG inhibitor (3); under ischemic conditions in the absence (4) or presence of: a PKG agonist (5); a nitric oxide (NO) donor (6) and a phosphodiesterase 5 (PDE5) inhibitor (7). Results: Under normoxia, the SFR was significantly attenuated by inhibition of PKG and remained unaltered with PKG activation. Ischemia induced a progressive decrease in myocardial contractility after stretch. Neither the PKG agonist nor the NO donor altered the myocardial response to stretch under ischemic conditions. However, the use of a PDE5 inhibitor in ischemia partially reversed the progressive deterioration in contractility. Conclusions: PKG activity is essential for the SFR. During ischemia, a progressive decline in the force is observed in response to acute myocardial stretch. This dysfunctional response can be partially reversed by the use of PDE5 inhibitors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7