title: Effect of ouabain in catecholamine-induced cardiac hypertrophy.
abstract: 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.
authors.affiliation: Department of Comparative Animal Physiology, Kossuth University, Debrecen, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Mészáros
authors.forename: B
authors.initials: B
authors.lastname: Pásztor
mesh_terms: 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
chemical_list: D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol