Function of the sarcoplasmic reticulum and expression of its Ca2"-ATPase gene in pressure overload-induced cardiac hypertrophy in the rat. Circ. Res

The reduction in Ca2+ concentration during diastole and relaxation occurs differently in normal hearts and in hypertrophied hearts secondary to pressure overload. We have studied some possible molecular mechanisms underlying these differences by examining the function of the sarcoplasmic reticulum and the expression of the gene encoding its Ca2-ATPase in rat hearts with mild and severe compensatory hypertrophy induced by abdominal aortic constric-tion. Twelve sham-operated rats and 31 operated rats were studied 1 month after surgery. Eighteen animals exhibited mild hypertrophy (left ventricular wt/body wt<2.6) and 13 animals severe hypertrophy (left ventricular wt/body wt>2.6). During hypertrophy we observed a decline in the function of the sarcoplasmic reticulum as assessed by the oxalate-stimulated Ca2+ uptake of homogenates of the left ventricle. Values decreased from 12.1+±1.2 nmol Ca2'/mg protein/min in sham-operated rats to 9.1±t1.5 and 6.7±+1.1 in rats with mild and severe hypertrophy, respectively (p <0.001 and p <0.001, respectively, vs. shams). This decrease was accompanied by a parallel reduction in the number of functionally active Ca2+-ATPase molecules, as determined by the level of Ca2+-dependent phosphorylated intermediate: 58.8+7.4 and 48.1+±13.5 pmol P/mg protein in mild and severe hypertrophy, respectively, compared with69.7+8.2 in shams (p<0.05 andp<0.01, respectively, vs. shams). Using Si nuclease mapping