Adrenoceptor blockade of the circulatory responses to intravenous isoproterenol

Linear log dose response curves were constructed of isoproterenol induced increases in heart rate and reductions in diastolic blood pressure from 6 normal healthy men. After propranolol and labetalol, such curves were shifted to the right in a parallel manner indicative of antagonism at both beta‐1 and beta‐2 adrenoceptor sites. Log dose‐response curves of isoproterenol‐induced increases in cardiac output before and after the antagonists followed a similar pattern as those of increases in heart rate and were found to be predominantly related to the changes in heart rate. Estimates of relative poteney at beta‐1 and beta‐2 sites fell in the range 4 to 6: 1 propranolol: labetalol. Serial measurement of the immediate eirculatory changes induced by propranolol (0.125 mg/kg intravenously) and labetalol (1.0 mg/kg intravenously) showed that their effeets were dissimilar. Propranolol indueed heart rate‐related reductions in cardiac output together with a small elevation in diastolie pressure, whereas labetalol reduced systolic and diastolie pressure without reducing heart rate or cardiac output. As propranolol and labetalol have qualitatively similar beta antagonist properties, the differenees in circulatory effeets seem to be due to the additional alpha adrenoceptor antagonist property of labetalol not possessed by propranolol. Adding the alpha blocking drug phentolamine to both propranolol and labetalol did not appear to influence the circulatory responses indueed by isoproterenol.