Effect of chronic digoxin on beta-adrenergic receptors in rabbits with heart failure

Abstract

This study investigated the effect of chronic digitalis glycoside use on beta-adrenergic sympathetic activities in heart failure. Twenty-two Japanese white rabbits were anesthetized by intravenous injection of chloral hydrate. Aortic regurgitation (AR) was produced by perforating aortic valves in 14 rabbits. Digoxin was given for 1 week to 7 rabbits with AR (AR + Dig) and saline to 7 rabbits with AR (AR + C). Sham operation was performed in the remaining 8 rabbits (S). The left ventricular end-diastolic pressure was higher in AR + C than S (p < 0.05). It was lower in AR + Dig than AR + C (p < 0.05). Cardiac output was lower in AR + C than S (p < 0.05). There was no difference between AR + Dig and S. Both the left ventricular end-diastolic and end-systolic diameters were larger in AR + C (p < 0.05) than S, but they were similar between AR + Dig and S. Plasma norepinephrine level was lower in AR + Dig than AR + C. Myocardial beta-adrenergic receptors number determined by radioligand binding assay using 30-800 pM 125I-iodocyanopindolol was lower in AR + C than S (28.8 +/- 7.9 vs. 69.9 +/- 12.3 fmol/mg protein, p < 0.05). It was higher in AR + Dig (39.9 +/- 9.8) than AR + C (p < 0.05). Myocardial norepinephrine content was lower in both AR + C (p < 0.05) and AR + Dig than S (p < 0.05). Thus, digitalis glycosides exert favorable effects on beta-adrenergic sympathetic activities in addition to the effects on hemodynamic variables in this animal model of heart failure.