Defective activity and isoform of the Na,K-ATPase in the dilated cardiomyopathic hamster.
The Na,K-ATPase function appears impaired in human heart failure with dilation; however little is known in animal model with idiopathic dilated cardiomyopathy. We studied Na,K-ATPase isoform composition and activity from cardiomyopathic hamsters of the MS 200 strain with pure dilated cardiomyopathy and compared them with those of healthy Syrian hamsters. 150-day-old male MS 200 Syrian hamsters (n = 16) and sex- and age-matched healthy Syrian hamsters (n = 15) were used. Antibodies specific for the three alpha-isoforms and against the beta1-isoform were used to study Na,K-ATPase isoform expression in ventricular myocardium. Na,K-ATPase activity was quantified in homogenate and membrane fractions. There was no significant change in left ventricular mass. Morphological examination revealed a decreased septum thickness in the dilated cardiomyopathy compared with control hamster. Idiopathic dilated cardiomyopathy in hamsters presented significantly reduced membrane alpha1 and beta1 abundances and reduced Na,K-ATPase activity (-35% vs. healthy control, p<0.05). Chronic heart failure had no effect on the Na,K-ATPase alpha2-subunit protein. We have demonstrated for the first time that dilated cardiomyopathy induces a specific reduction of both membrane alpha1- and beta1-isoform abundance and Na,K-ATPase activity in hamsters similar to those previously reported in human dilated heart failure.
Paganelli
F
F
Department of Cardiology, H pital Nord, Marseille, France.
Mougenot
R
R
Maixentt
J M
JM
D000818:Animals; D001835:Body Weight; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000473:pathology; D002458:Cell Fractionation; D006224:Cricetinae; D004073:Digitoxigenin / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009929:Organ Size; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D004073:Digitoxigenin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase