DISTRIBUTION OF AIRWAY CONTRACTILE RESPONSES WITHIN THE MAJOR DIAMETER BRONCHI DURING EXOGENOUS BRONCHOCONSTRICTION

Publisher Website
Google Scholar
Abstract
The distribution of bronchoconstrictor responses within airway generations zero to 6 was studied by tantalum bronchography during exogenous bronchoconstriction with methacholine (MCh), prostaglandin F2.alpha.(PGF2.alpha.), norepinephrine (NE), and the thromboxane mimetic U-46619 [(15S)-hydroxyl-11 .alpha., 9 .alpha.-(epoxymethano)prosta-5Z,13E-dienoic acid] in 12 mongrel dogs undergoing vagotomy and beta-adrenergic blockade. Dose-response curves to each agonist were generated in random order, and tantalum bronchograms and simultaneous measurements of pulmonary resistance (RL) and dynamic pulmonary compliance (Cdyn) were obtained at the plateau of the response of each dose of agonist after intravenous (iv) infusion. At 5 .times. 10-7 mol/kg, NE (after .beta.-adrenergic blockade) caused an increase to 254 .+-. 27.3%, PGF2.alpha. to 368 .+-. 50.0%, U-46619 to 522 .+-. 98.5%, and MCh to 1,204 .+-. 173% of baseline in RL. However, airway diameter changes within the major diameter airways varied substantially for each agonist. Methacholine caused substantial contraction in all airways. Neither NE nor U-46619 caused significant airway narrowing in generations zero or 1, although both agonists caused > 30% narrowing in sixth generation airways. Prostaglandin F2.alpha. (5 .times. 10-7 mol/kg) cause an increase in RL of > 350%; however, this was accompanied by an .apprx. 10% increase (dilation) in airway diameter in generation 1 through generation 4 airways and an approximate 25% narrowing in generation 6 airways. We demonstrate that both alpha-adrenergic agonists and thromboxane analog cause substantial bronchococonstriction in situ in the central airways of the lung. We also demonstrate that for comparable changes in RL, the distribution of bronchoconstrictor responses within the major diameter bronchi varies substantially for each airway with each contractile agonist.