Functionally Opposing Roles of Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase in the Regulation of Cardiac Contractility

István Szokodi; Risto Kerkelä; Anna‐Maria Kubin; Balázs Sármán; Sampsa Pikkarainen; Attila Kónyi; Iván Horváth; Lajos Papp; Miklós Tóth; Réka Skoumal; Heikki Ruskoaho

doi:10.1161/circulationaha.107.758623

September 30, 2008CirculationOpen Access

Functionally Opposing Roles of Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase in the Regulation of Cardiac Contractility

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Why the study?

Does pharmacological modulation of ERK1/2 and p38-MAPK pathways alter the inotropic effect of endothelin-1 in isolated perfused rat hearts?

Structured PICO

Does pharmacological modulation of ERK1/2 and p38-MAPK pathways alter the inotropic effect of endothelin-1 in isolated perfused rat hearts?

P

Population

Isolated perfused rat hearts

I

Intervention

Infusion of endothelin-1 (ET-1) (1 nmol/L) for 10 minutes, with pharmacological inhibition of ERK1/2, epidermal growth factor receptor kinase, Na(+)-H(+) exchanger 1, or p38-MAPK

C

Comparator

ET-1 infusion alone

O

Outcome

Cardiac contractility and phosphorylation of ERK1/2, p90RSK, and phospholambansurrogate

ERK1/2 mediates a positive inotropic response to ET-1 that is counterbalanced by p38-MAPK, suggesting that selective modulation of these pathways could support cardiac contractility.

Implication

Hypothesis-generating in rat hearts; leaves open whether selective ERK1/2 or p38-MAPK modulation can enhance contractility in human HF.

Discussion

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Cite This Study

Szokodi et al. (2008) studied this question.

synapsesocial.com/papers/6a821da48ef2ccdd49f25249 https://doi.org/10.1161/circulationaha.107.758623

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Functionally Opposing Roles of Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase in the Regulation of Cardiac Contractility

Structured PICO

Implication

Discussion

Cite This Study

Functionally Opposing Roles of Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase in the Regulation of Cardiac Contractility

Structured PICO

Implication

Discussion

Cite This Study

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