Altered cardiac mechanism and sarcoplasmic reticulum function in pressure overload-induced cardiac hypertrophy in rats.

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we examined the hypothesis that alterations in SR function occur during the development of hypertrophy of the left ventricle (LV) induced in rats by pressure overload secondary to abdominal aortic coarctation. Ten days, 4 and 8 weeks after the operation, hemodynamic parameters were measured using a catheter-tip manometer. The SR vesicles of hypertrophic LV (group A) and sham-operated LV (group S) at each stage were used to study Ca2+ release and uptake, and to characterize the ryanodine receptor. Moderate hypertrophy was observed in group A even at the earliest stage. Systolic LV pressure and peak +dP/dt were significantly increased in group A. There were no significant change in diastolic LV pressure in either group at any stage. Hemodynamic data indicated that LV function in group A was enhanced during the development of the hypertrophy. The amount of Ca2+ release and uptake, and the number of ryanodine binding sites on the SR were higher in group A than in group S at both early and middle stages. However, 8 weeks after the operation, SR activity was normal, even though cardiac function was still augmented. Our results indicated that LV hypertrophy induced by pressure overload is associated with altered intracellular Ca2+ regulation, as reflected by the increased Ca2+ release and uptake functions of the SR and the quantitative change in the number of ryanodine receptors during the early stages of the development of hypertrophy. Therefore, alterations in the SR Ca2+ transport capacity could account, at least in part, for the alterations in E-C coupling seen in hypertrophy.