title: Stretch-elicited Na+/H+ exchanger activation: the autocrine/paracrine loop and its mechanical counterpart.
abstract: 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.
authors.affiliation: Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 1900, La Plata, Argentina. cicmes@infovia.com.ar <cicmes@infovia.com.ar>
authors.forename: Horacio E
authors.initials: HE
authors.lastname: Cingolani
authors.forename: Néstor G
authors.initials: NG
authors.lastname: Pérez
authors.forename: Burket
authors.initials: B
authors.lastname: Pieske
authors.forename: Dirk
authors.initials: D
authors.lastname: von Lewinski
authors.forename: María C
authors.initials: MC
authors.lastname: Camilión de Hurtado
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D016232:Endothelins / Q000502:physiology; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*
chemical_list: D016232:Endothelins; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II