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 nmolof 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 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.

[1]  J. Scheuer,et al.  Studies of subcellular control factors in hearts of uremic rats. , 1976, The Journal of laboratory and clinical medicine.

[2]  R. Webb,et al.  Altered calcium sequestration by subcellular fractions of vascular smooth muscle from spontaneously hypertensive rats. , 1976, Journal of molecular and cellular cardiology.

[3]  J. Kuo,et al.  Depressed cardiac cyclic GMP-dependent protein kinase in spontaneously hypertensive rats and its further depression by guanethidine , 1976, Nature.

[4]  M. Entman,et al.  The rate of calcium uptake into sarcoplasmic reticulum of cardiac muscle and skeletal muscle. Effects of cyclic AMP-dependent protein kinase and phosphorylase b kinase. , 1976, Biochimica et biophysica acta.

[5]  M. Kirchberger,et al.  Effects of adenosine 3':5'-monophosphate-dependent protein kinase on sarcoplasmic reticulum isolated from cardiac and slow and fast contracting skeletal muscles. , 1976, The Journal of biological chemistry.

[6]  E. Landon,et al.  Energy-dependent calcium uptake activity of microsomes from the aorta of normal and hypertensive rats. , 1975, Biochimica et biophysica acta.

[7]  J. Gergely,et al.  Effect of cross-reinnervation on physiological parameters and on properties of myosin and sarcoplasmic reticulum of fast and slow muscles of the rabbit , 1975, The Journal of general physiology.

[8]  H. Suga,et al.  Hemodynamics of spontaneously hypertensive rats in conscious state. , 1975, Japanese heart journal.

[9]  O. Isaksson,et al.  Consequences of myocardial structural adaptation on left ventricular compliance and the Frank-Starling relationship in spontaneously hypertensive rats. , 1975, Acta physiologica Scandinavica.

[10]  A. Katz,et al.  Adenosine 3':5'-monophosphate-dependent protein kinase-catalyzed phosphorylation reaction and its relationship to calcium transport in cardiac sarcoplasmic reticulum. , 1974, The Journal of biological chemistry.

[11]  E. Morkin,et al.  Adenosine 3′, 5′‐Monophosphate‐Dependent Membrane Phosphorylation: A Possible Mechanism for the Control of Microsomal Calcium Transport in Heart Muscle , 1974 .

[12]  M. Entman,et al.  Analysis of calcium binding and release by canine cardiac relaxing system (sarcoplasmic reticulum). The use of specific inhibitors to construct a two-component model for calcium binding and transport. , 1973, The Journal of biological chemistry.

[13]  J. Murray,et al.  Molecular control mechanisms in muscle contraction. , 1973, Physiological reviews.

[14]  M. Pfeffer,et al.  Hemodynamic and Myocardial Function in Young and Old Normotensive and Spontaneously Hypertensive Rats , 1973, Circulation research.

[15]  S. Salmons,et al.  Synthesis by fast muscle of myosin light chains characteristic of slow muscle in response to long-term stimulation. , 1973, Nature: New biology.

[16]  H. L. Wray,et al.  Cyclic adenosine 3',5'-monophosphate-stimulated protein kinase and a substrate associated with cardiac sarcoplasmic reticulum. , 1973, The Journal of biological chemistry.

[17]  D. Walsh,et al.  Protein kinases: aspects of their regulation and diversity. , 1973, Recent progress in hormone research.

[18]  A. Katz,et al.  Cyclic adenosine 3',5'-monophosphate-dependent protein kinase stimulation of calcium uptake by canine cardiac microsomes. , 1972, Journal of molecular and cellular cardiology.

[19]  A. Scarpa,et al.  The Effect of Calcium Ionophores on Fragmented Sarcoplasmic Reticulum , 1972, The Journal of general physiology.

[20]  E. Krebs,et al.  Purification and Characterization of a Protein Inhibitor of Adenosine 3',5'-Monophosphate-dependent Protein Kinases , 1971 .

[21]  Thompson Wj,et al.  Multiple cyclic nucleotide phosphodiesterase activities from rat brain , 1971 .

[22]  J. Suko,et al.  Intracellular Calcium and Myocardial Contractility: III. Reduced Calcium Uptake and Atpase of the Sarcoplasmic Reticular Fraction Prepared from Chronically Failing Calf Hearts , 1970, Circulation research.

[23]  A. Schwartz,et al.  Rate of Calcium Binding and Uptake in Normal Animal and Failing Human Cardiac Muscle: MEMBRANE VESICLES (RELAXING SYSTEM) AND MITOCHONDRIA , 1969, Circulation research.

[24]  S Ebashi,et al.  Control of muscle contraction , 1969, Quarterly Reviews of Biophysics.

[25]  K. Weber,et al.  The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. , 1969, The Journal of biological chemistry.

[26]  B B Brodie,et al.  A simple, sensitive method for the assay of adenyl cyclase. , 1968, The Journal of pharmacology and experimental therapeutics.

[27]  G. Siegel,et al.  Sodium-potassium-activated adenosine triphosphatase of Electrophorus electric organ. IV. Modification of responses to sodium and potassium by arsenite plus 2,3-dimercaptopropanol. , 1967, The Journal of biological chemistry.

[28]  M. Hess,et al.  Activity of the Vesicular Calcium Pump in the Spontaneously Failing Heart‐Lung Preparation , 1967, Circulation research.