Enhanced calcium mobilization in rat ventricular myocytes during the onset of pressure overload-induced hypertrophy.
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 Ca(2+) 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). Ca(2+) transient amplitude was significantly augmented in the PO-2d group. In the PO-7d group, intracellular Ca(2+) concentration ([Ca(2+)](i)) was reduced during diastole, and mechanical twitch relaxation (but not [Ca(2+)](i) decline) was slowed. In PO groups, fractional sarcoplasmic reticulum (SR) Ca(2+) release at a twitch, SR Ca(2+) content, SR Ca(2+) loss during diastole, and SR-dependent integrated Ca(2+) flux during twitch relaxation were significantly greater than in sham-operated groups, whereas the relaxation-associated Ca(2+) flux carried by the Na(+)/Ca(2+) exchanger was not significantly changed. In the PO-7d group, mRNA levels of cardiac isoforms of SR Ca(2+)-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 Ca(2+) cycling between SR and cytosol early after PO imposition, even before hypertrophy development. Increase in SR Ca(2+) uptake may contribute to enhancement of excitation-contraction coupling (augmented SR Ca(2+) content and release) and protection against arrhythmogenesis due to buildup of [Ca(2+)](i) during diastole.
Carvalho
Beatriz M R
BM
Centro de Engenharia Biomédica, Universidade Estadual de Campinas, Caixa Postal 6040, 13084-971 Campinas, SP, Brazil.
Bassani
Rosana A
RA
Franchini
Kleber G
KG
Bassani
José W M
JW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003971:Diastole / Q000502:physiology; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015398:Signal Transduction / Q000502:physiology; D013599:Systole / Q000502:physiology; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban