Ipratropium bromide potentiates bronchoconstriction induced by vagal nerve stimulation in the guinea-pig.
In anaesthetised guinea-pigs, bronchoconstriction induced by vagal nerve stimulation was potentiated by low doses of the antimuscarinic bronchodilator drug, ipratropium (0.01-1.0 microgram/kg); the maximum effect was obtained with 1.0 microgram/kg which doubled the bronchoconstriction. When the dose was increased above 1.0 microgram/kg potentiation no longer occurred; instead the vagally induced bronchoconstriction was antagonised. This was accompanied by reduction in the bronchoconstriction and bradycardia induced by i.v. acetylcholine, due to blockade of post-junctional muscarinic receptors in the airways and heart. With 10 micrograms/kg ipratropium responses elicited both by vagal stimulation and by exogenous acetylcholine were abolished. The results show that ipratropium is an antagonist for pre-junctional muscarinic inhibitory receptors on pulmonary parasympathetic nerves and also confirm its potent antagonist actions on post-junctional muscarinic receptors in the airway smooth muscle. The effect of ipratropium in the lung depends, therefore, on the balance between the pre- and post-junctional effects.
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D003251:Constriction, Pathologic; D004357:Drug Synergism; D004558:Electric Stimulation; D006168:Guinea Pigs; D009241:Ipratropium / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology*
D001286:Atropine Derivatives; D009241:Ipratropium