Direct vasodilatation by labetalol in anaesthetized dogs

1 The effects of several doses of labetalol (0.03 to 1 mg/kg) given intravenously and into the vertebral artery were examined in anaesthetized dogs. Labetalol produced to immediate (5 min) change in blood pressure or heart rate when given by either route, with one exception. Heart rate increased after the first dose (0.03 mg/kg i.v.) of labetalol. By contrast, clonidine (1 micrograms/kg) elicited an immediate and prolonged fall in blood pressure and heart rate when given into the vertebral artery, but not intravenously. 2 In the isolated perfused gracilis muscle of the dog, following alpha- and beta-adrenoceptor blockade, intra-arterial injections of labetalol (0.3 to 10 mg) or diazoxide (0.3 to 1 mg) produced decreases in perfusion pressure that were dose-related in both magnitude and duration. The doses of labetalol and diazoxide required to produce a half-maximal vasodilatation were 1.5 mg and 0.7 mg respectively. 3 In adrenalectomized, vagotomized spinal dogs, both labetalol (0.1 to 1 mg/kg i.v.) and hydralazine (1 mg/kg i.v.) elicited a fall in blood pressure without changing heart rate or cardiac output. 4. These results suggest that the hypotension produced by systemically administered labetalol does not involve an action in the brain. It may involve instead a direct vasodilatation of resistance blood vessels, since labetalol in sufficient amounts, directly dilates resistance vessels and lowers blood pressure in dogs devoid of adrenergic tone. Direct vasodilatation may be a component of the hypotensive action of labetalol.