© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Stretch-elicited Na+/H+ exchanger activation: the autocrine/paracrine loop and its mechanical counterpart
aCentro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 1900 La Plata, Argentina
bAbteilung Kardiologie und Pneumologie, Univesität Göttingen, Göttingen, Germany
* Corresponding author. Tel.: +54-221-483-4833; fax: +54-221-425-5861. cicmes{at}infovia.com.ar
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.
KEYWORDS Angiotensin; Endothelins; Na/Ca-exchanger; Na/H-exchanger; Stretch/m-e coupling
1 Established investigators of Consejo Nacional de Investigaciones Científicas y Técnicas (Conicet) Argentina.
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