Effect of ouabain in catecholamine-induced cardiac hypertrophy.
Changes in the sensitivity to ouabain of the hypertrophied myocardium were studied in isolated left ventricular trabeculae of rat heart using conventional microelectrode technique, and in anaesthetized rats using limb-lead electrocardiography (ECG). Hypertrophy was induced by administration of 5 mg/kg isoprenaline once daily for 7 days. The age-matched normal control rats received the same volume of 0.9% NaCl solution. The heart weight to body weight ratio increased from 3.23 +/- 0.07 mg/kg to 4.37 +/- 0.12 mg/kg, which means a 35% hypertrophy. The action potential duration at 50% repolarization (APD50) was 25.1 +/- 2.4 ms in normal case and 63.5 +/- 4.6 ms in hypertrophy. The S-T interval of the ECG was 24.9 +/- 1.9 ms in normal rats and 64.4 +/- 3.4 ms in hypertrophy. The toxic effect of ouabain was studied by determining the concentrations of the drug at which arrhythmogenic transient depolarizations (TDs; in microelectrode experiments) or sustained ventricular tachyarrhythmias (VTAs; in ECG experiments) appeared. The dose of ouabain inducing TDs was 345 +/- 25 microM in normal case and 630 +/- 40 microM in hypertrophy. In ECG studies, the dose inducing VTAs was 19.1 +/- 3.6 mg/kg in normal rats and 34.3 +/- 3.1 mg/kg in hypertrophy. The results suggest that catecholamine-induced cardiac hypertrophy damages the membrane-bound Na+, K(+)-ATPase, thus decreasing the number of the ouabain binding sites, which consequently, makes the myocardium membrane more insensitive to ouabain.
Mészáros
J
J
Department of Comparative Animal Physiology, Kossuth University, Debrecen, Hungary.
Pásztor
B
B
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000201:enzymology; D004562:Electrocardiography; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013610:Tachycardia / Q000139:chemically induced
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol