Mechanisms underlying the increase in force and Ca2+ transient that follow stretch of cardiac muscle: A possible explanation of the Anrep effect

Bernardo V. Alvarez, Néstor G. Pérez, Irene L. Ennis, María C. Camilión De Hurtado, Horacio E. Cingolani

Research output: Contribution to journalArticlepeer-review


Myocardial stretch produces an increase in developed force (DF) that occurs in two phases: the first (rapidly occurring) is generally attributed to an increase in myofilament calcium responsiveness and the second (gradually developing) to an increase in [Ca2+](i). Rat ventricular trabeculae were stretched from ≃88% to ≃98% of L(max), and the second force phase was analyzed. Intracellular pH, [Na+](i), and Ca2+ transients were measured by epifluorescence with BCECF-AM, SBFI-AM, and fura-2, respectively. After stretch, DF increased by 1.94±0.2 g/mm2 (P<0.01, n=4), with the second phase accounting for 28±2% of the total increase (P<0.001, n=4). During this phase, SBFI(340/380) ratio increased from 0.73±0.01 to 0.76±0.01 (P<0.05, n=5) with an estimated [Na+](i) rise of ≃6 mmol/L. [Ca2+] transient, expressed as fura-2(340/380) ratio, increased by 9.2±3.6% (P<0.05, n=5). The increase in [Na+](i) was blocked by 5-(N-ethyl- N-isopropyl)-amiloride (EIPA). The second phase in force and the increases in [Na+](i) and [Ca2+](i) transient were blunted by AT1 or ET(A) blockade. Our data indicate that the second force phase and the increase in [Ca2+](i) transient after stretch result from activation of the Na+/H+ exchanger (NHE) increasing [Na+](i) and leading to a secondary increase in [Ca2+](i) transient. This reflects an autocrine-paracrine mechanism whereby stretch triggers the release of angiotensin II, which in turn releases endothelin and activates the NHE through ETA receptors.

Original languageEnglish (US)
Pages (from-to)716-722
Number of pages7
JournalCirculation research
Issue number8
StatePublished - Oct 15 1999


  • Anrep effect
  • Ca transient
  • Myocardial stretch
  • Na/Ca exchanger
  • pH(i)

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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