Pressure-induced cardiac hypertrophy: changes in Na+,K+-ATPase and glycoside actions in cats.
Effects of myocardial hypertrophy caused by pressure overload on sarcolemmal Na+,K+-ATPase and positive inotropic action of strophanthidin were examined in cats. Partial ligation of the main pulmonary artery for four weeks resulted in right ventricular hypertrophy with no significant changes in left ventricular muscle. Hypertrophy was associated with a reduction in the number of active Na+,K+-ATPase units. Affinity of the remaining enzyme for [3H]ouabain was unchanged. No apparent right or left shift in dose-response curve for the positive inotropic effect of strophanthidin was observed and toxic concentrations of strophanthidin were unchanged; however, the degree of the positive inotropic effect produced by high concentrations of strophanthidin was significantly smaller in hypertrophied muscle. Moreover, decreases in developed tension rather than tachyarrhythmias was the predominant form of toxicity observed in hypertrophied muscle. These results indicate that myocardial hypertrophy reduces the number of active Na+,K+-ATPase units per milligram protein, decreases maximal positive inotropic effect of strophanthidin, and alters the prevailing form of strophanthidin toxicity.
D000818:Animals; D001665:Binding Sites; D002301:Cardiac Glycosides / Q000633:toxicity*; D006332:Cardiomegaly / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D002415:Cats; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000378:metabolism; D011312:Pressure; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis*; D013327:Strophanthidin / Q000633:toxicity
D002301:Cardiac Glycosides; D010042:Ouabain; D013327:Strophanthidin; D000254:Sodium-Potassium-Exchanging ATPase