Inhibition of the carotid sinus reflex by the chronic administration of propranolol.
1. The changes in heart rate and arterial pressure produced by the intravenous injection of isoprenaline (0.5 mug/kg), noradrenaline (1.0 mug/kg), phenylethylamine (0.5 mg/kg), amphetamine (0.5 mg/kg) and by bilateral occlusion of the carotid arteries and by stimulation of the central ends of both vagus nerves have been recorded in groups of dogs anaesthetized with pentobarbitone.2. The acute intravenous injection of propranolol (1 mg/kg) reduced the increases in heart rate produced by the six procedures, the increases in arterial pressure in response to the last five procedures and the decrease in pressure produced by isoprenaline.3. This decrease produced by propranolol in the pressor responses resulted from a reduction in the increases in cardiac output elicited by the five procedures and has been attributed to blockade of cardiac adrenergic beta-receptors.4. Three groups of dogs were pretreated for 6 weeks by the oral administration of either placebo, propranolol 50 mg/kg daily or propranolol 10 mg/kg twice daily. The responses to the six test procedures were obtained 17-24 hr after the last dose of propranolol, when only minimal blockade of adrenergic beta-receptors was present. In the propranolol-treated groups, the pressor response to carotid occlusion but not to the other test procedures was significantly reduced.5. The pressor response to carotid occlusion was not reduced in a fourth group of dogs given a single dose of propranolol (50 mg/kg) 24 hr before the test procedures.6. The mechanism of this selective reduction in the pressor response to occlusion of the carotid arteries is not clear. It is suggested that it may contribute to the hypotensive action of propranolol in man during prolonged oral administration.