Defective calcium transport by cardiac sarcoplasmic reticulum in spontaneously hypertensive rats

Ca²⁺ uptake and binding and Ca²⁺ ATPase activity of cardiac sarcoplasmic reticulum (SR) from spontaneously hypertensive rats (SHR) were compared to that obtained from normotensive Wistar Kyoto (WKY) rats. Ca²⁺ uptake (172±3.7 nmol/mg of protein per min in WKY vs. 112±2.6 in the SHR, P < 0.001) and binding (154±3.0 nmol/mg per min in WKY vs. 101±1.8 in the SHR. P < 0.01) were decreased in the SHR. Ca²⁺ ATPase activity, however, was significantly higher in the SHR (118±3.1 nmol of P per mg of protein per min vs. 86±1.1 in the WKY, P < 0.001), suggesting 'uncoupling' of the ATPase to calcium transport. Cyclic AMP dependent phosphorylation of SR was significantly decreased in SHR (0.71±0.05 vs. 0.32±0.07 nmol of P/mg of protein per 10 min, P < 0.001) and there was an excellent correlation between cyclic AMP induced phosphorylation of SR and Ca²⁺ uptake (r = 0.81). Differences in both cyclic AMP dependent phosphorylation and Ca²⁺ uptake between the two groups were evident at 10 wk and increased progressively to 22 wk of age. Differences in endogenous cyclic AMP dependent protein kinase activity may partly explain the decreased Ca²⁺ transport in SHR.