| Left ventricular hypertrophy (LVH) refers to the compensatory enlargement of the heart aimed at reducing the stress caused by pressure overload (PO) or volume overload (VO) and maintaining adequate blood supply to tissues and organs; however, sustained hypertrophy leads to heart failure. The mechanisms underlying the transition from hypertrophy to heart failure are poorly understood. The aim of this study was to examine the involvement of cardiac sarcoplasmic reticulum (SR) in the development of contractile dysfunction due to PO or VO. We hypothesized that hypertrophy due to PO or VO will induce cardiac contractile dysfunction that will be associated with changes in the function of the SR. We also hypothesized that the alterations in SR calcium (Ca2+) handling and its regulation due to PO will be distinct from those induced by VO.; PO and VO were induced surgically by performing abdominal aortic banding and aortoeaval shunt procedures, respectively. Cardiac structure and function were assessed via echocardiography at 2, 4, 16, and 28 weeks following the surgeries. SR function and its regulation were also examined. Over the course of the study, PO rats exhibited progressive thickening of LV walls while VO rats demonstrated progressive dilatation of LV cavity. Rats subjected to PO exhibited signs of diastolic dysfunction from 4 weeks onwards while systolic dysfunction became evident only after 28 weeks. In contrast, in VO rats, only systolic function was impaired at 16 as well as at 28 weeks. SR Ca 2+-uptake was enhanced in PO as early as 4 weeks, but not in the VO group. SR Ca2+-uptake was elevated at 16 weeks, which corresponded to higher levels of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) (in both PO and VO) and increased phosphorylation of phospholamban (PLB) at Ser16 and Thr17 (only in PO). At 28 weeks, SR Ca2+-uptake normalized to control levels in PO hearts while it still remained elevated in VO. Ratio of PLB:SERCA2a was unchanged in both PO and VO at 28 weeks. The observed reduction of the Ca2+-uptake at 28 weeks in PO could be due to the increased activities of the phosphatases. Interestingly, in VO, reduced kinase and increased phosphatase activities did not impair SR function. We conclude that the progression of hypertrophy due to PO and VO in rats is accompanied by differential alterations in cardiac structure and function, as well as in SR function and its regulation. |
