Abstract
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.
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The authors are established investigators of CONICET, Argentina.
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Cingolani, H.E., Ennis, I.L., Aiello, E.A. et al. Role of autocrine/paracrine mechanisms in response to myocardial strain. Pflugers Arch - Eur J Physiol 462, 29–38 (2011). https://doi.org/10.1007/s00424-011-0930-9
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DOI: https://doi.org/10.1007/s00424-011-0930-9