The effects of propranolol treatment on adrenoceptor reactivity and on cardiac myosin ATPase activity have been studied. Eight mongrel dogs weighing 8 to 14 Kg were given propranolol orally 3 times daily (10 mg/Kg/day) for 2 weeks. Although the levels of propranolol were effective and there was a significant decrease in resting heart rate, there was no evidence of a rebound adrenoceptor hypersensitivity after abrupt withdrawal of propranolol treatment. The responsiveness of cardiovascular systems to 1-isoproterenol (1-ISO) was significantly attenuated 15 hrs after the last medication, but it did not differ from the premedication levels 6 days after discontinuation of medication. The effects of 1-ISO on adenylate cyclase activity in the myocardial membrane preparations were not significantly different between the 3 groups (no medication, 1 day and 6 days after discontinuation). With propranolol treatment, though a rise in total plasma catecholamine (norepinephrine, epinephrine, dopamine) levels was the predominant change, there were no definite changes in respective catecholamines. Serum triiodothyronine (T3) increased during medication in 7 of the 8 animals and decreased after medication. Calcium-activated and K+-activated myosin ATPase activity in the inner and outer layers of the left ventricular wall were uniform in unmedicated dogs, and propranolol produced no significant effects. No reliable evidence for propranolol withdrawal syndromes was provided in the present study.
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