Concurrent antagonism of isoproterenol and norepinephrine after labetalol.

Labetalol reduces blood pressure in normotensive and hypertensive subjects. The effects of a therapeutic dose of intravenous labetalol upon the cardiovascular responses to intravenous isoproterenol and norepinephrine in 6 normotensive subjects were studied in order to investigate the drug's mode of action. Before labetalol, intravenous isoproterenol increased heart rate and reduced diastolic blood pressure in a dose-dependant manner; likewise, intravenous norepinephrine increased both systolic and diastolic pressure. The order of administration of these agonists was randomized between the subjects before and after labetalol. Following labetalol (1.5 mg/kg intravenously) the effects of isoproterenol were antagonized such that cumulative log-dose response curves of mean isoproterenol-induced increases in heart rate and reductions in diastolic pressure were shifted to the right in a parallel manner to approximately the same extent. At the same time, the mean norepinephrine-induced increases in systolic and diastolic blood pressure were also antagonized in a competitive manner. These responses were compared with others in the same subjects under the same conditions and it was concluded that the antihypertensive effect of labetalol is explained by concurrent blockade of alpha-and beta-adrenoceptors.

RCT Entities:   Population Interventions Outcomes