Stretch-elicited Na+/H+ exchanger activation: The autocrine/paracrine loop and its mechanical counterpart

Horacio E. Cingolani, Néstor G. Pérez, Burket Pieske, Dirk Von Lewinski, María C. Camilión De Hurtado

Research output: Contribution to journalReview articlepeer-review


The stretch of the cardiac muscle is immediately followed by an increase in the contraction strength after which occurs a slow force increase (SFR) that takes several minutes to fully develop. The SFR was detected in a wide variety of experimental preparations including isolated myocytes, papillary muscles and/or trabeculae, left ventricle strips of failing human myocardium, in vitro isovolumic and in vivo volume-loaded hearts. It was established that the initial increase in force is due to an increase in myofilament Ca2+ responsiveness, whereas the SFR results from an increase in the Ca2+ transient. However, the mechanism(s) for this increase in the Ca2+ transient has remained undefined until the proposal of Na+/H+ exchanger (NHE) activation by stretch. Studies in multicellular cardiac muscle preparations from cat, rabbit, rat and failing human heart have shown evidence that the stretch induces a rise in intracellular Na+ ([Na+]i) through NHE activation, which subsequently leads to an increase in Ca2+ transient via reverse-mode Na+/Ca2+ (NCX) exchange. These experimental data agree with a theoretical ionic model of cardiomyocytes that predicted an increased Na+ influx and a concurrent increase in Ca2+ entry through NCX as the cause of the SFR to muscle stretch. However, there are aspects that await definitive demonstration, and perhaps subjected to species-related differences like the possibility of an autocrine/paracrine loop involving angiotensin II and endothelin as the underlying mechanism for stretch-induced NHE activation leading to the rise in [Na+]i and reverse-mode NCX.

Original languageEnglish (US)
Pages (from-to)953-960
Number of pages8
JournalCardiovascular research
Issue number4
StatePublished - Apr 1 2003
Externally publishedYes


  • Angiotensin
  • Endothelins
  • Na/Ca-exchanger
  • Na/H-exchanger
  • Stretch/m-e coupling

ASJC Scopus subject areas

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


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