The Anrep effect: 100 years later

Horacio E. Cingolani, Néstor G. Pérez, Oscar H. Cingolani, Irene L. Ennis

Research output: Contribution to journalReview articlepeer-review

93 Scopus citations


Myocardial stretch elicits a rapid increase in developed force, which is mainly caused by an increase in myofilament calcium sensitivity (Frank-Starling mechanism). Over the ensuing 10-15 min, a second gradual increase in force takes place. This slow force response to stretch is known to be the result of an increase in the calcium transient amplitude and constitutes the in vitro equivalent of the Anrep effect described 100 years ago in the intact heart. In the present review, we will update and discuss what is known about the Anrep effect as the mechanical counterpart of autocrine/ paracrine mechanisms involved in its genesis. The chain of events triggered by myocardial stretch comprises 1) release of angiotensin II, 2) release of endothelin, 3) activation of the mineralocorticoid receptor, 4) transactivation of the epidermal growth factor receptor, 5) increased formation of mitochondria reactive oxygen species, 6) activation of redox-sensitive kinases upstream myocardial Na+/H+ exchanger (NHE1), 7) NHE1 activation, 8) increase in intracellular Na+ concentration, and 9) increase in Ca2+ transient amplitude through the Na+/Ca2+ exchanger. We will present the experimental evidence supporting each of the signaling steps leading to the Anrep effect and its blunting by silencing NHE1 expression with a specific small hairpin interference RNA injected into the ventricular wall.

Original languageEnglish (US)
Pages (from-to)H175-H182
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2
StatePublished - Jan 15 2013


  • Angiotensin ii
  • Nhe1
  • Slow force response
  • Stretch
  • Transactivation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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