Altered Sarcoplasmic Reticulum Ca2+ATPase Gene Expression in Congestive Heart Failure: Effect of Chronic Norepinephrine Infusion

We have examined the ryanodine receptor, Ca2+–ATPase, calsequestrin and phospholamban mRNA levels in the left ventricles of pacing-induced heart failure and norepinephrine infusion dogs. The heart failure dogs showed a decrease in the levels of ryanodine receptor and Ca2+–ATPase mRNAs. Norepinephrine infusion caused a reduction of Ca2+–ATPase mRNA but no change in ryanodine receptor mRNA. There was a corresponding reduction of the immunoreactive Ca2+–ATPase protein levels in both heart failure and norepinephrine infusion animals compared to controls. In contrast, the mRNAs of calsequestrin and phospholamban were unchanged in dogs with either congestive heart failure or norepinephrine infusion. Thus, since norepinephrine infusion and congestive heart failure produced similar reductions of Ca2+–ATPase mRNA and protein, we postulate that the down-regulation of Ca2+–ATPase in congestive heart failure may be caused, at least in part, by sympathetic stimulation that occurs in heart failure.