Role of autocrine/paracrine mechanisms in response to myocardial strain

Horacio E. Cingolani, Irene L. Ennis, Ernesto A. Aiello, Néstor G. Pérez

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


Myocardial strain triggers an autocrine/paracrine mechanism known to participate in myocardial hypertrophy development. After the onset of stretch, there is a rapid augmentation in developed tension due to an increase in myofilament calcium sensitivity (the Frank Starling mechanism) followed by a gradual increase in tension over the next 10-15 min. This second phase is called the slow force response (SFR) to stretch and is known to be the result of an increase in calcium transient amplitude. In the present review, we will discuss what is known thus far about the SFR, which is the in vitro equivalent of the Anrep effect and the mechanical counterpart of the autocrine/paracrine mechanism elicited by myocardial stretch. The chain of events triggered by myocardial stretch comprises: (1) release of angiotensin II, (2) release/formation of endothelin, (3) NADPH oxidase activation and transactivation of the EGFR, (4) mitochondrial reactive oxygen species production, (5) activation of redox-sensitive kinases, (6) NHE-1 hyperactivity, (7) increase in intracellular Na+ concentration, and (8) increase in Ca2+ transient amplitude through the Na+/Ca2+ exchanger. The evidence for each step of the intracellular signaling pathway leading to the development of SFR and their relationship with the mechanisms proposed for cardiac hypertrophy development will be analyzed.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Issue number1
StatePublished - Jul 2011
Externally publishedYes


  • Angiotensin
  • Contractility
  • Endothelin
  • Epidermal growth factor
  • Hypertrophy
  • Oxidative stress
  • Sodium-hydrogen exchange
  • Stretch

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


Dive into the research topics of 'Role of autocrine/paracrine mechanisms in response to myocardial strain'. Together they form a unique fingerprint.

Cite this