Increased Na+/Ca2+ Exchanger Expression/Activity Constitutes a Point of Inflection in the Progression to Heart Failure of Hypertensive Rats |
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Authors: | Jesica S Rodriguez J Omar Velez Rueda Margarita Salas Romina Becerra Mariano N Di Carlo Matilde Said Leticia Vittone Gustavo Rinaldi Enrique L Portiansky Cecilia Mundi?a-Weilenmann Julieta Palomeque Alicia Mattiazzi |
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Institution: | 1. Centro de Investigaciones Cardiovasculares, CONICET-La Plata, Facultad de Medicina, Universidad Nacional de La Plata, La Plata, Argentina.; 2. Laboratorio de Análisis de Imágenes, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina.; The University of Manchester, United Kingdom, |
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Abstract: | Spontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. Ca2+-handling alterations are known to occur in SHR. However, the putative modifications of Ca2+-handling proteins during the progression to heart failure (HF) are not well established. Moreover, the role of apoptosis in SHR is controversial. We investigated intracellular Ca2+, Ca2+-handling proteins and apoptosis in SHR vs. control Wistar rats (W) from 3 to 15 months (mo). Changes associated with the transition to HF (i.e. lung edema and decrease in midwall fractional shortening), occurred at 15 mo in 38% of SHR (SHRF). In SHRF, twitch and caffeine-induced Ca2+ transients, significantly decreased relative to 6/9 mo and 15 mo without HF signs. This decrease occurred in association with a decrease in the time constant of caffeine-Ca2+ transient decay and an increase in Na+/Ca2+ exchanger (NCX) abundance (p<0.05) with no changes in SERCA2a expression/activity. An increased Ca2+-calmodulin-kinase II activity, associated with an enhancement of apoptosis (TUNEL and Bax/Bcl2) was observed in SHR relative to W from 3 to 15 mo. Conclusions: 1. Apoptosis is an early and persistent event that may contribute to hypertrophic remodeling but would not participate in the contractile impairment of SHRF. 2. The increase in NCX expression/activity, associated with an increase in Ca2+ efflux from the cell, constitutes a primary alteration of Ca2+-handling proteins in the evolution to HF. 3. No changes in SERCA2a expression/activity are observed when HF signs become evident. |
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