Labetalol protects against the potentiation by propranolol of the bronchospasm to norepinephrine in guinea-pigs.

The increase in airway obstruction observed in asthmatics after treatment with beta-adrenergic blockers may be attributed to an unopposed alpha-adrenergic activity. Labetalol is an antihypertensive agent with beta-adrenoreceptor and alpha-adrenoreceptor blocking properties. Labetalol does not cause a bronchospasm in human asthmatics. Norepinephrine (0.025-0.1 mg/kg, i.v.) caused a bronchospasm in guinea-pigs after the blockade of beta-adrenoreceptors with propranolol (0.1-1 mg/kg, i.v.), but not after beta-blockade with labetalol (0.1-10 mg/kg, i.v.). Labetalol significantly protected against the bronchospasm induced by norepinephrine in the presence of propranolol. The bronchospasm induced by norepinephrine was inhibited by alpha-adrenergic blockade with phentolamine (0.03-3 mg/kg, i.v.), but not by blockade of receptors for histamine, acetylcholine or sulfidopeptide leukotrienes or by inhibition of cyclooxygenase activity. The lack of a bronchospasm after stimulation of alpha 2-receptors with B-HT 920 suggests that the bronchospasm to norepinephrine was due to the activation of alpha-adrenoreceptors on airway smooth muscle. The more desirable pulmonary profile of labetalol compared with other beta-blockers may be due, in part, to the interaction of labetalol with both beta- and alpha-adrenoreceptors.