Distribution of airway contractile responses within the major diameter bronchi during exogenous bronchoconstriction.
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 X 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 greater than 30% narrowing in sixth generation airways. Prostaglandin F2 alpha (5 X 10(-7) mol/kg) cause an increase in RL of greater than 350%; however, this was accompanied by an approximately 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 bronchoconstriction in situ in the central air-ways of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001980:Bronchi / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology; D001995:Bronchography; D015237:Dinoprost; D004285:Dogs; D005260:Female; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology
D008688:Methacholine Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D011460:Prostaglandins F; D016210:Methacholine Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D009638:Norepinephrine