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This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/H1803    most recent 01345.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Carvalho, B. M. R. Articles by Bassani, J. W. M. Search for Related Content PubMed PubMed Citation Articles by Carvalho, B. M. R. Articles by Bassani, J. W. M.

Enhanced calcium mobilization in rat ventricular myocytes during the onset of pressure overload-induced hypertrophy

¹Departamento de Engenharia Biomédica/Faculdade de Engenharia Elétrica e de Computação, ²Centro de Engenharia Biomédica, and ³Departamento de Clínica Médica/Faculdade de Ciências Médicas Universidade Estadual de Campinas, Campinas, Brazil

Submitted 20 December 2005 ; accepted in final form 19 April 2006

Early cardiovascular changes evoked by pressure overload (PO) may reveal adaptive strategies that allow immediate survival to the increased hemodynamic load. In this study, systolic and diastolic Ca²⁺ cycling was analyzed in left ventricular rat myocytes before (day 2, PO-2d group) and after (day 7, PO-7d group) development of hypertrophy subsequent to aortic constriction, as well as in myocytes from time-matched sham-operated rats (sham group). Ca²⁺ transient amplitude was significantly augmented in the PO-2d group. In the PO-7d group, intracellular Ca²⁺ concentration ([Ca²⁺]_i) was reduced during diastole, and mechanical twitch relaxation (but not [Ca²⁺]_i decline) was slowed. In PO groups, fractional sarcoplasmic reticulum (SR) Ca²⁺ release at a twitch, SR Ca²⁺ content, SR Ca²⁺ loss during diastole, and SR-dependent integrated Ca²⁺ flux during twitch relaxation were significantly greater than in sham-operated groups, whereas the relaxation-associated Ca²⁺ flux carried by the Na⁺/Ca²⁺ exchanger was not significantly changed. In the PO-7d group, mRNA levels of cardiac isoforms of SR Ca²⁺-ATPase (SERCA2a), phospholamban, calsequestrin, ryanodine receptor, and NCX were not significantly altered, but the SERCA2a-to-phospholamban ratio was increased 2.5-fold. Moreover, greater sensitivity to the inotropic effects of the -adrenoceptor agonist isoproterenol was observed in the PO-7d group. The results indicate enhanced Ca²⁺ cycling between SR and cytosol early after PO imposition, even before hypertrophy development. Increase in SR Ca²⁺ uptake may contribute to enhancement of excitation-contraction coupling (augmented SR Ca²⁺ content and release) and protection against arrhythmogenesis due to buildup of [Ca²⁺]_i during diastole.

sarcoplasmic reticulum; excitation-contraction coupling; relaxation; -adrenergic responsiveness

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