Effects of intravenous and aerosol nifedipine on prostaglandin F2 alpha and histamine-induced bronchoconstriction in anesthetized dogs

PE Malo, MA Wasserman and RL Griffin

The effect of nifedipine, a calcium slow channel blocking drug, was investigated by varying routes of administration in a canine model of pharmacologically induced bronchoconstriction. Control bronchopulmonary responses, i.e., increases in pulmonary resistance (RL) and decreases in dynamic lung compliance were accomplished by aerosols of prostaglandin F2 alpha and histamine in normal pentobarbital- anesthetized beagles. When infused i.v. within the range 200 to 400 micrograms/kg, nifedipine afforded significant protection vs. RL changes due to prostaglandin F2 alpha (84--89% inhibition). Aerosol pretreatment by nifedipine (0.1 and 1.0%) also produced significant inhibition in RL changes caused by prostaglandin F2 alpha. A single i.v. injection (200 micrograms/kg) of nifedipine provided significant protection against RL changes due to a histamine challenge for 240 min. The onset of protection occurred within 15 min and maximum protection occurred during the 60 to 90-min period after the single injection of nifedipine. A single aerosol pretreatment of nifedipine (0.1%) significantly blocked RL changes against successive histamine aerosol challenges at 15-, 30- and 60-min time periods. Infused nifedipine failed to have any relaxant effect on the resting base line of either RL or dynamic lung compliance, whereas aerosolized nifedipine did decrease resting airway tone intrinsically, although not significantly. In addition, cardiovascular side effects by the aerosol route were slight compared to those observed by the i.v. route of nifedipine. Therefore, delivery of a calcium channel antagonist by either the aerosol or i.v. route can inhibit pharmacologically induced bronchoconstriction.

Volume 221, Issue 2, pp. 410-415, 05/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics