Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 291, Issue 4, Pages H1803-H1813Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01345.2005
Keywords
sarcoplasmic reticulum; excitation-contraction coupling; relaxation; beta-adrenergic responsiveness
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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 beta-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.
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