ALTERED CARDIAC MECHANISM AND SARCOPLASMIC-RETICULUM FUNCTION IN PRESSURE OVERLOAD-INDUCED CARDIAC-HYPERTROPHY IN RATS

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucia l role in the regulation of intracellular Ca2+, Its functional propert ies are central to the excitation-contraction (E-C) cycle of cardiac m uscle. In this study, we examined the hypothesis that alterations in S R function occur during the development of hypertrophy of the left ven tricle (LV) induced in rats by pressure overload secondary to abdomina l aortic coarctation, Ten days, 4 and 8 weeks after the operation, hem odynamic 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 cha racterize 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. Hemodyn amic data indicated that LV function in group A was enhanced during th e development of the hypertrophy. The amount of Ca2+ release and uptak e, 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 we eks after the operation, SR activity was normal, even though cardiac f unction 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 uptak e functions of the SR and the quantitative change in the number of rya nodine receptors during the early stages of the development of hypertr ophy, Therefore, alterations in the SR Ca2+ transport capacity could a ccount, at least in part, for the alterations in E-C coupling seen in hypertrophy. (C) 1997 Academic Press Limited.