Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats

Abstract

Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal.