Effect of chronic propranolol treatment and withdrawal on norepinephrine and tyrosine hydroxylase in sympathetic tissues
Atkins, F.; Nicolosi, G.L.; Beck, L.
Archives Internationales de Pharmacodynamie et de Therapie 254(2): 271-281
1981
ISSN/ISBN: 0003-9780 PMID: 6121541 Document Number: 181225
Abrupt discontinuation of propranolol in patients with coronary artery disease may lead to untoward ischemic events. The explanation for this clinical syndrome has been thought to be related to a physiological sympathetic rebound. To investigate a biochemical basis for this hypothesis we administered propranolol (5 mg/kg s.c.) twice daily to guinea-pigs for 2 weeks. Heart rates gradually declined during treatment and after cessation of the drug returned to control level without evidence of rebound. Left ventricular and right atrial norepinephrine levels were unchanged in the withdrawal period. Tyrosine hydroxylase activity was unchanged in the right atrium but had declined significantly in the left ventricle at 96 hr. Tyrosine hydroxylase activity was unchanged in the stellate ganglion and adrenal gland. Thus, we did not find any alterations in catecholamine metabolism compatible with a sympathetic rebound state.