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

Abstract

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 β-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.