REDUCED CONCENTRATION OF MYOCARDIAL NA-ATPASE IN HUMAN AORTIC-VALVE DISEASE AS WELL AS OF NA+,K+-ATPASE AND CA2+-ATPASE IN RODENTS WITH HYPERTROPHY(,K+)

Myocardial Na+,K+-ATPase was studied in patients with aortic valve dis ease, and myocardial Na+,K+- and Ca2+-ATPase were assessed in spontane ously hypertensive rats (SHR) and hereditary cardiomyopathic hamsters using methods ensuring high enzyme recovery. Na+,K+-ATPase was quantif ied by [H-3]ouabain binding to intact myocardial biopsies from patient s with aortic valve disease, Aortic stenosis, regurgitation and a comb ination hereof were compared with normal human heart and were associat ed with reductions of left ventricular [H-3]ouabain binding site conce ntration (pmol/g wet weight) of 56, 46 and 60%, respectively (p < 0.01 ). Na+,K+- and Ca2+-ATPases were quantified by K+- and Ca2+-dependent p-nitrophenyl phosphatase (pNPPase) activity determinations in crude m yocardial homogenates from SHR and hereditary cardiomyopathic hamsters . When SHR were compared to age-matched Wistar Kyoto (WKY) rats an inc rease in heart-body weight ratio of 75% (p < 0.001) was associated wit h reductions of K+- and Ca2+-dependent pNPPase activities (mu mol/min/ g wet weight) of 42 (p < 0.01) and 27% (p < 0.05), respectively. When hereditary cardiomyopathic hamsters were compared to age-matched Syria n hamsters an increase in heart-body weight ratio of 69% (p < 0.001) w as found to be associated with reductions in K+- and Ca2+-dependent pN PPase activities of 50 (p < 0.001) and 26% (p = 0.05), respectively. T he reductions in Na+,K+- and Ca2+-ATPases were selective in relation t o overall protein content and were not merely the outcome of increased myocardial mass relative to Na+,K+-and Ca2+-pumps. In conclusion, myo cardial hypertrophy is in patients associated with reduced Na+,K+-ATPa se concentration and in rodents with reduced Na+,K+- and Ca2+-ATPase c oncentrations. This may be of importance for development of heart fail ure and arrhythmia in hypertrophic heart disease.