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 less than 0.001) and binding (154 +/- 3.0 nmol/mg per min in WKY vs. 101 +/- 1.8 in the SHR, P less than 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 less than 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 less than 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 weeks and increased progressively to 22 weeks of age. Differences in endogenous cyclic AMP-dependent protein kinase activity may partly explain the decreased Ca2+ transport in SHR.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000201:enzymology; D000242:Cyclic AMP / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D010750:Phosphoproteins; D011506:Proteins; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D000251:Adenosine Triphosphatases; D002118:Calcium