Effects of digoxin on acetylcholine and norepinephrine concentrations in rat myocardium

The influence of digoxin on the autonomic nervous system was studied in rats by examining its effects on the levels of acetylcholine (Ach), a parasympathetic marker, and norepinephrine (NE), a sympathetic marker, in the rat myocardium. Ach and NE were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). Digoxin was injected subcutaneously every day for 4 weeks. The administration of 0.35, 0.75, and 2.5 mg/kg of digoxin reduced Ach concentrations in the right atrium to about 80-90% of the control value. However, there was no change in the activity of choline acetyltransferase (ChAT) or acetylcholinesterase (AchE), or in the concentration of choline (Ch). Injection of 0.1 mg/kg of digoxin had no significant effect on Ach concentration. When 0.75 and 2.5 mg/kg of digoxin were injected, there was a significant increase in NE concentration in the right atrium. Neither 0.1 nor 0.35 mg/kg caused any changes. Digoxin (0.75 and 2.5 mg/kg) increased heart rate to about 110% of the control values. Thus, high doses of digoxin increase the NE concentration but decrease the Ach concentration in the rat heart, and these changes might be related to functional changes in the autonomic nervous system.