Increased [Na.sup.+]/[Ca.sup.2+] exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats

• Published in: PloS one 2014-04, Vol.9 (4)
• Main Authors: Rodriguez, Jesica S, Rueda, J. Omar Velez, Salas, Margarita, Becerra, Romina, Di Carlo, Mariano N, Said, Matilde, Vittone, Leticia, Rinaldi, Gustavo, Portiansky, Enrique L, Mundina-Weilenmann, Cecilia, Palomeque, Julieta, Mattiazzi, Alicia
• Format: Article
• Language: English
• Subjects: Apoptosis; Caffeine; Calcium-binding proteins; Care and treatment; Diagnosis; Health aspects; Heart failure; Hypertension; Nutritional aspects; Risk factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096400

Spontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. [Ca.sup.2+]-handling alterations are known to occur in SHR. However, the putative modifications of [Ca.sup.2+]-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 [Ca.sup.2+],[Ca.sup.2+]-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 [Ca.sup.2+] 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-[Ca.sup.2+] transient decay and an increase in [Na.sup.+]/[Ca.sup.2+] exchanger (NCX) abundance (p < 0.05) with no changes in SERCA2a expression/activity. An increased [Ca.sup.2+]-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 [Ca.sup.2+] efflux from the cell, constitutes a primary alteration of [Ca.sup.2+]-handling proteins in the evolution to HF. 3. No changes in SERCA2a expression/activity are observed when HF signs become evident.