The Autocrine/Paracrine Loop After Myocardial Stretch: Mineralocorticoid Receptor Activation

Author(s): Irene L. Ennis, Ernesto A. Aiello, Horacio E. Cingolani, Nestor G. Perez

Journal Name: Current Cardiology Reviews

Volume 9 , Issue 3 , 2013

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The stretch of cardiac muscle increases developed force in two phases. The first phase, which occurs rapidly, constitutes the well-known Frank-Starling mechanism and it is generally attributed to enhanced myofilament responsiveness to Ca2+. The second phase or slow force response (SFR) occurs gradually and is due to an increase in the calcium transient amplitude as a result of a stretch-triggered autocrine/paracrine mechanism. We previously showed that Ca2+ entry through reverse Na+/Ca2+ exchange underlies the SFR, as the final step of an autocrine/paracrine cascade involving release of angiotensin II/endothelin, and a Na+/H+ exchanger (NHE-1) activation-mediated rise in Na+. In the present review we mainly focus on our three latest contributions to the understanding of this signalling pathway triggered by myocardial stretch: 1) The finding that an increased production of reactive oxygen species (ROS) from mitochondrial origin is critical in the activation of the NHE-1 and therefore in the genesis of the SFR; 2) the demonstration of a key role played by the transactivation of the epidermal growth factor receptor; and 3) the involvement of mineralocorticoid receptors (MR) activation in the stretch-triggered cascade leading to the SFR. Among these novel contributions, the critical role played by the MR is perhaps the most important one. This finding may conceivably provide a mechanistic explanation to the recently discovered strikingly beneficial effects of MR antagonism in humans with cardiac hypertrophy and failure.

Keywords: Myocardial stretch, slow force response, Anrep effect, mineralocorticoid receptor, reactive oxygen species, Na+/H+ exchanger activation.

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Article Details

Year: 2013
Page: [230 - 240]
Pages: 11
DOI: 10.2174/1573403X113099990034
Price: $65

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