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beta-Blocking actions of orally administered Kö 1400 and tiprenolol, new beta-blocking agents, were studied in unanesthetized rats and dogs, using a fall of blood pressure and an increase in heart rate produced by isoproterenol as a measure of beta-receptor activation. Blood pressure was recorded from the aorta of the dog and the caudal artery of rat via indwelling catheter, and heart rate of the dog was recorded by a cardiotachometer triggered by R waves of the lead II electrocardiogram. Mean resting blood pressure was 116 mmHg in rats and 93 mmHg in dogs, and heart rate was 99 beats/min in dogs. Isoproterenol (0.5 microgram/kg) was injected via indwelling venous catheter. Kö 1400, tiprenolol and propranolol inhibited the hypotension and tachycardia induced by isoproterenol at an oral dose level of 2 mg/kg or more. beta-blocking action in these preparations was found to be tiprenolol greater than Kö 1400 greater than propranolol. Pharmacological half life of tiprenolol was longer than that of propranolol, whereas that of Kö 1400 was shorter. No selectivity of beta-blocking actions was observed with all three beta-blockers. These findings are in agreement with the results obtained in isolated atrial and tracheal preparations of the guinea pig.

Drug effects on blood pressure and heart rate in unanesthetized animals