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PubMed1988

Reflex decrease of histamine-induced bronchoconstriction after laryngeal stimulation in asthmatic patients.

The aim of this work was to determine if the nonadrenergic noncholinergic nervous system can be reflexly activated in asthmatic patients by stimulating the vocal cords. The stimulation was produced by a cytology brush passed through a bronchoscope previously introduced transnasally and positioned just above the epiglottis. The subjects were premedicated with cholinergic blockers, and bronchoconstriction was induced by inhalation of histamine. In 11 experiments performed on six patients, vocal cords stimulation resulted in a decreased RL from 8.4 +/- 1.0 to 6.3 +/- 0.8 cm H2O.L-1.s (mean +/- SE) (p less than 0.01). To assess the possible contribution of circulating catecholamines to this decrease, plasma epinephrine and norepinephrine levels were measured in six experiments, before and 30 s, 1, 3, and 5 min after the stimulation. Pulmonary resistance fell from 10.0 +/- 1.3 to 7.6 +/- 0.9 cm H2O.L-1.s (mean +/- SE) (p less than 0.05) 30 s and to 7.9 +/- 0.9 cm H2O.L-1.s (p less than 0.05) 60 s after stimulation. Epinephrine and norepinephrine levels increased slightly but not significantly throughout the experiment. We conclude that in asthmatic patients, as in normal subjects, stimulation of the vocal cords produces a reflex decrease in histamine-induced bronchoconstriction which is modulated by the nonadrenergic noncholinergic nervous system.

Administration, Inhalation↗
PubMed1989

The influence of refractoriness to adenosine 5'-monophosphate on allergen-provoked bronchoconstriction in asthma.

Repeated bronchoprovocation with adenosine 5'-monophosphate (AMP) in atopic, nonasthmatic subjects produces a state of refractoriness to the nucleotide that may be due either to depletion of preformed mediators from airway mast cells or down-regulation of purinoceptors on the surface of these cells. To investigate this further, we compared the effect on immediate allergen-provoked bronchoconstriction of preceding repeated challenges with histamine and AMP in eight atopic, mildly asthmatic subjects. In three successive AMP concentration-response studies, the geometric mean PC20 AMP increased from 275.3 to 1154.3 (p less than 0.01) and 1976.7 (p less than 0.01) mg/ml, respectively, whereas no significant similar increase in PC20 occurred with repeated histamine challenges. Refractoriness to AMP was not associated with any significant decrease in airways responsiveness to histamine. When compared with the response after repeated provocation with inhaled histamine, repeated exposure of the airways to AMP potentiated, rather than inhibited, immediate allergen-induced bronchoconstriction by a mean 57 +/- 22.6% (p less than 0.05) when the data were expressed as the area under the FEV1-time response curve. The ability of airways that have been rendered less responsive to inhaled AMP to exhibit an increased response to allergen suggests that tachyphylaxis to AMP is unlikely to be caused by depletion of preformed mast cell-derived mediators such as histamine.

Adenosine Monophosphate↗
PubMed1989

Expiratory glottic widening in asthmatic subjects during exercise-induced bronchoconstriction.

Glottic caliber is modulated in a way that optimizes the airway resistance and the work of breathing. The midexpiratory glottic narrowing that normally occurs during tidal breathing is enhanced during histamine- or methacholine-induced airway narrowing. Exercise is associated with increased ventilatory demand and midexpiratory glottic widening in healthy subjects. However, the relative contribution of glottic aperture to airflow limitation during exercise-induced asthma is unknown. Consequently, we used the acoustic reflection technique to test whether a decrease in midexpiratory glottic size occurred also during exercise-induced bronchoconstriction in seven asthmatic subjects. Exercise resulted in a 38 +/- 16% (SD) fall in FEV1 from the baseline value (p less than 0.001) and a significant increase in midexpiratory glottic cross-sectional area from 1.89 +/- 0.45 cm2 before to 2.36 +/- 0.71 cm2 during bronchoconstriction (p less than 0.05). This midexpiratory glottic widening was also associated with increased tidal flow rates. We conclude that in marked contrast to airway obstruction induced by histamine or methacholine, exercise-induced asthma is associated with midexpiratory glottic widening, which occurs concomitantly with a decrease in lower airway caliber. We suggest that modulation of glottic aperture during acute asthma is heterogeneous and depends partly on the initiating stimulus.

Adult↗
PubMed1989

Is a myogenic response involved in deep inspiration-induced bronchoconstriction in asthmatics?

The mechanisms by which a deep inspiration (DI) induces bronchoconstriction in some asthmatic patients remain unclear. As a calcium-dependent myogenic response could be involved, we examined the effect of a potent voltage-dependent calcium channel (VDC) antagonist, nifedipine (20 mg administered sublingually) versus placebo, on the DI-induced change in plethysmographic specific airway conductance (SGaw) in six asthmatic patients and six healthy controls both before and after a bronchial challenge with methacholine (MCh). In the asthmatic group, when compared to those receiving placebo, nifedipine significantly reduced the decrease in SGaw induced by the DI at baseline (-34.2 +/- 5.6 and -12.7 +/- 3.6%, respectively) but it had no significant effect on mean SGaw baseline values (0.096 +/- 0.018 and 0.075 +/- 0.015 cm H2O-1.s.-1, respectively). When airway tone was increased with MCh, the DI-induced change in SGaw was reduced and nifedipine then had no further effect. In the control group, nifedipine had no significant effect on the weak changes in SGaw induced by the DI before or after the bronchial challenge. We conclude that nifedipine reduces DI-induced bronchoconstriction only in subjects with asthma and without altering baseline tone in airway smooth muscle. We suggest that this effect of nifedipine could be explained by the existence of a myogenic response in asthma, caused by the conversion of airway smooth muscle from intermediate to single unit function.

Airway Resistance↗
PubMed1990

Bronchoalveolar lavage cell and mediator responses to hyperpnea-induced bronchoconstriction in the guinea pig.

We studied the association between bronchoconstriction and bronchoalveolar lavage (BAL) cell and mediator profiles in unsensitized guinea pigs (GP) after hyperpnea to determine whether eicosanoids or histamine are released during hyperpnea-induced bronchoconstriction (HIB). Twelve animals were challenged with warm, moist (WM) air (T = 35 degrees C, relative humidity = 91 to 94%), 14 with room dry (RD) air (T = 25 degrees C, relative humidity less than 2.1%), and 18 with cold, dry (CD) air (T = 7 degrees C, relative humidity less than 2.1%). Lung resistance (RL) and elastance (EL) were recorded at baseline and at 2-min intervals after hyperventilation. Challenges were terminated either when a greater than or equal to 100% increase in RL was observed postchallenge or after completion of a 135 breaths/min challenge if RL did not increase. BAL was performed, and samples were analyzed for total cells, white cell and epithelial cell differentials, total protein concentration, and mediator content.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1990

Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma.

Histamine and certain cyclooxygenase products of arachidonic acid have been implicated as mediators of inflammation and are potent constrictors of human airways. Because asthma may represent manifestations of chronic inflammation of the airways, the levels of histamine and six prostanoid mediators were measured in airway fluids obtained by bronchoalveolar lavage (BAL) of 12 normal, 11 allergic rhinitic, and 15 asymptomatic, allergic asthmatic subjects. Simultaneous profiling of prostanoid mediators in individual samples was performed using gas chromatography-mass spectrometry. Levels of PGD2, 9 alpha,11 beta-PGF2 and PGF2 alpha were 12 to 22 times higher in asthmatic than in normal subjects (p less than 0.01), with concentrations in airway fluids of asthmatic subjects after correction for dilution of 3.8, 0.5, and 1.4 nanomolar, respectively. Levels of PGD2 and 9 alpha,11 beta-PGF2 were increased nearly tenfold in asthmatic subjects compared with those in rhinitic subjects (p less than 0.01), distinguishing the subjects with lower airway disease from those with another atopic condition. Histamine levels were increased fourfold in asthmatic subjects compared with those in normal subjects (p less than 0.001); however, similar increases were found in rhinitic subjects. We conclude that elevated levels of multiple mediators with potent bronchoconstricting activity are present in the airways of subjects with mild asthma, indicating that even mild disease is associated with evidence of airway inflammation. The interactions of bronchoconstricting mediators and airway inflammation may play important roles in the pathogenesis of asthma.

Adult↗
PubMed1990

Effect of inhaled furosemide on metabisulfite- and methacholine-induced bronchoconstriction and nasal potential difference in asthmatic subjects.

To evaluate the hypothesis that furosemide inhibits indirect bronchoconstrictor challenges by altering airway epithelial ion transport, we studied its effects on indirect bronchoconstriction induced by inhaled metabisulfite (MBS) and nasal potential difference (PD) in seven subjects with mild asthma. Its effect on direct bronchoconstriction by the inhaled muscarinic agonist methacholine (MC) was studied in six of these subjects. Each subject inhaled furosemide, 30 mg, in a randomized, double-blind, placebo-controlled fashion immediately before challenge with MBS (0.3 to 160 mg/ml in increasing doubling concentrations) and, in another study, MC (0.125 to 32 mg/ml) aerosols from a nebulizer attached to a dosimeter. PC20MBS and PC20MC, the concentration of each agent needed to lower FEV1 by 20%, were calculated by linear interpolation of the log dose-response curves. Furosemide had no effect on resting lung function, but it caused a significant threefold reduction in sensitivity to MBS (PC20MBS: GM +/- GSEM, 15.1 +/- 1.6 mg/ml after placebo and 40.7 +/- 1.7 mg/ml after furosemide; p less than 0.001) with a protective index of 64.8 +/- 10.7%. Furosemide caused no change in sensitivity to MC (PC20 MC:GM +/- GSEM, 2.37 +/- 1.61 mg/ml after placebo and 2.19 +/- 1.751 mg/ml after furosemide; NS). In a third study, furosemide, 30 mg, and placebo were inhaled through the nose in a randomized double-blind fashion immediately prior to inhalation of a PC20 concentration of MBS through the nose. Nasal PD was measured before and after placebo or furosemide, and again after MBS inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Interfacing between spontaneous breathing and mechanical ventilation affects ventilation-perfusion distributions in experimental bronchoconstriction.

The effect of interfacing between spontaneous and mechanical ventilation on ventilation-perfusion (VA/Q) distributions was determined during pressure-support ventilation (PSV) and in the presence and absence of spontaneous breathing during biphasic positive airway pressure (BIPAP) in 10 pigs with methacholine-induced bronchoconstriction. Whereas BIPAP without spontaneous breathing provides full and PSV breath-to-breath synchronized ventilatory support, BIPAP allows unrestricted spontaneous breathing throughout the mechanical cycle. Compared with BIPAP with and without spontaneous breathing, PSV effected an increase in ventilatory rate (p < 0.05) and a higher minute ventilation (VE) (p < 0.05). Spontaneous breathing during BIPAP accounted for 15 +/- 1% of the VE and increased cardiac output (CO) from 4.5 +/- 0.2 to 5.3 +/- 0.2 L/min (p < 0.05), Pao2 from 55 +/- 3 to 80 +/- 4 mm Hg (p < 0.05), and oxygen delivery (DO2) from 442 +/- 39 to 630 +/- 43 ml/min (p < 0.05). PSV did not increase CO, Pao2, and DO2. Spontaneous breathing did not affect oxygen consumption. During BIPAP spontaneous breathing accounted for a 15 +/- 2% decrease (p < 0.05) in blood flow to shunt units and a 16 +/- 2% increase (p < 0.05) in the perfusion of normal VA/Q units. Perfusion of shunt and normal VA/Q units was similar during PSV and BIPAP without spontaneous breathing. Dead space ventilation decreased with spontaneous breathing during BIPAP by 12% compared with PSV (p < 0.05). Dispersion of ventilation distribution was lowest during BIPAP. Uncoupling of spontaneous and mechanical ventilation during BIPAP improved gas exchange by allowing better VA/Q matching during experimental bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Measurements of airway edema in allergic bronchoconstriction in the guinea pig.

We tested the hypothesis that acute bronchoconstriction in the guinea pig was associated with airway edema by measuring extravascular water in the airways and lung parenchyma. Thirty guinea pigs were immunized with egg albumin and 30 nonimmunized guinea pigs served as controls. An aerosolized challenge with egg albumin produced acute respiratory distress in the immunized but not in the control animals. The animals were killed (6 per group) immediately and 1, 3, 6, and 24 h after the challenge, and the extravascular water content of the airways and parenchyma was measured. We found that airway extravascular water varied from 3.90 +/- 0.58 to 3.12 +/- 0.25 g/g dry tissue in the control group and from 3.61 +/- 0.41 to 3.79 +/- 0.33 g/g dry tissue in the experimental group. A two-way analysis of variance showed no difference between the groups. Similar results were found in parenchymal samples. We concluded that allergic bronchoconstriction in the guinea pig is not associated with airway edema.

Airway Obstruction↗
PubMed1982

Effect of the oronasal breathing route on sulfur dioxide-induced bronchoconstriction in exercising asthmatic subjects.

We undertook a study to determine how the oronasal breathing route affects the bronchoconstrictor response to sulfur dioxide (SO2) inhaled by asthmatic subjects during exercise. In 6 subjects, we compared the changes in specific airway resistance (SRaw) caused by breathing humidified air through a mouthpiece during 5 min of exercise on a bicycle ergometer (550 kpm/min) to the changes caused by breathing humidified air plus 0.5 ppm of SO2, (a) through a mouthpiece (oral breathing), (b) by facemask (oronasal breathing), and (c) by facemask with the mouth occluded (nasal breathing) during exercise. Breathing humidified air plus 0.5 ppm of SO2 through a mouthpiece or by facemask during exercise significantly increased SRaw in all 6 subjects, and breathing humidified air plus 0.5 PPM of SO2 by facemask with the mouth occluded significantly increased SRaw in 5 of 6 subjects. The increase in SRaw caused by breathing humidified air plus 0.5 PPM of SO2 through a mouthpiece was not significantly different from the increase caused by breathing SO2 by facemask (p greater than 0.05), but was significantly greater than the increase caused by breathing SO2 by facemask with the mouth occluded (p less than 0.05). These results indicate that although nasal breathing partially protected against SO2-induced bronchoconstriction in our subjects, both oral and oronasal breathing of low concentrations of SO2 during exercise can cause significant bronchoconstriction in people with asthma.

Adult↗
PubMed1983

The protective effect of inhaled chlorpheniramine and atropine on bronchoconstriction stimulated by airway cooling.

We examined the role of histamine release and reflex bronchoconstriction in the bronchoconstriction stimulated by airway cooling. In 8 asthmatic subjects, dose-response curves were determined to isocapnic hyperventilation of cold air 30 min after inhalation of chlorpheniramine maleate (18 mg nebulized during tidal breathing), 2 doses of atropine sulphate (3 mg and 18 mg nebulized), or placebo. Treatments were given on separate days, in random order and under double-blind conditions. The bronchial antihistamine and anticholinergic actions of chlorpheniramine were determined by the effect on histamine and methacholine dose-response curves on another 4 days. Chlorpheniramine was selective as an antagonist against histamine; it increased the mean provocation concentration of histamine to reduce the FEV1 by 20% (PC20) 14.2-fold but increased the mean PC20 methacholine only 1.85-fold. Atropine in the 3-mg dose, previously shown to increase the PC20 methacholine at least 100-fold, had no effect on heart rate or saliva output in contrast to 18 mg, which significantly reduced saliva output and increased heart rate. Chlorpheniramine caused no bronchodilation and a small 1.28-fold increase in the amount of respiratory heat exchange needed to reduce the FEV1 by 10% (PD10RHE). Atropine caused maximal bronchodilation after 3 mg and a dose-dependent increase in PD10RHE (1.16-fold increase after 3 mg and 1.32-fold increase after 18 mg atropine). The effect of chlorpheniramine and atropine 18 mg on PD10RHE was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Effect of allergic bronchoconstriction on airways epithelial permeability to large polar solutes in the guinea pig.

The effect of allergic bronchoconstriction on the permeability of the airway mucosa to large hydrophilic polar solutes was investigated in the guinea pig. After specific antigen (ovalbumin) challenge, there was a significant increase in the plasma levels of horseradish peroxidase (HRP) (molecular weight, approximately 40,000 daltons), 3H-dextran (approximately 10,000 daltons), and 14C-mannitol (approximately 182 daltons) compared with that in control animals aerosol-challenged with a nonspecific protein, lactoglobulin. The morphologic correlates of this enhanced transepithelial permeability after ovalbumin challenge appeared to be (1) increased HRP penetration of the epithelial tight junctions (p less than 0.001), and (2) increased mucus discharge from surface lining goblet cells. We conclude that antigen-induced bronchoconstriction leads to an increase in tracheobronchial permeability to macromolecules, and this effect is likely to be mediated by an increased paracellular as well as transcellular vesicular movement of large polar solutes across the airway epithelial barrier.

Animals↗
PubMed1983

Sulfur dioxide-induced bronchoconstriction in freely breathing, exercising, asthmatic subjects.

The purpose of this study was to determine whether 0.50 ppm sulfur dioxide (SO2) in filtered air causes bronchoconstriction in freely breathing asthmatic subjects exercising at a moderately heavy work rate. Ten volunteers who had mild asthma breathed air containing no SO2 or containing 0.50 ppm SO2 In an exposure chamber as they exercised for 5 min on a cycle ergometer at a work rate of 750 kilopond meters/min (about 125 watts). We determined their specific airway resistance by body plethysmography before and after exercise. Specific airway resistance increased by 13.55 +/- 9.18 cm H2O X s (mean +/- SD) when subjects exercised and breathed 0.50 ppm SO2 but only by 2.24 +/- 2.34 when they exercised and breathed air without SO2 (p less than 0.005). Thus, 0.50 ppm SO2 causes significant bronchoconstriction in freely breathing asthmatics during moderately heavy exercise.

Adult↗
PubMed1986

The effects of parasympathectomy on serotonin-induced bronchoconstriction in the cat.

We studied the contribution of neural influences, in particular, the nonadrenergic, noncholinergic inhibitory system, on the modulation of airway responses to serotonin (5-HT) in the anesthetized and mechanically ventilated cat. Airway responses were assessed by measurement of pulmonary resistance (RL). Parasympathectomy (PS) caused a variable increase in bronchoconstriction in 9 of 10 cats (n = 10) that had received pretreatment intravenously with atropine (3 mg/kg) and propranolol (2 mg/kg); PS performed following pretreatment with phentolamine (2 mg/kg), propranolol, and atropine led to an increase in bronchoconstriction in only 2 of 6 cats. Dose-response curves to aerosolized 5-HT were performed in one group of cats (n = 5) before and 30 min after PS and in control group (n = 6). Both groups of animals were pretreated intravenously with atropine, propranolol, and phentolamine. The concentration of aerosolized 5-HT that was necessary to double pulmonary resistance (ED200RL) was significantly reduced from 0.117 to 0.062 mg/ml (p less than 0.01) by PS, in contrast to control cats in which ED200RL during 2 consecutive dose-response curves (0.076 and 0.087 mg/ml, respectively) did not change significantly. We conclude that there is neural modulation of airway responses to infused 5-HT through an alpha-adrenergic pathway and that an additional inhibitory nonadrenergic, noncholinergic neural influence is demonstrable in the response to aerosolized 5-HT.

Aerosols↗
PubMed1986

The inhibition of sulfur dioxide-induced bronchoconstriction in asthmatic subjects by cromolyn is dose dependent.

To determine whether the inhibitory effect of cromolyn on sulfur dioxide-induced bronchoconstriction is dose dependent, we compared the effects of treatment with 200 mg of cromolyn, with 20 mg of cromolyn, and with placebo on the rise in specific airway resistance provoked by inhalation of serially increasing concentrations of sulfur dioxide (0.25 to 8.0 ppm) in 10 asthmatic subjects. The geometric mean concentration of sulfur dioxide needed to cause an increase in SRaw of 8 L X cm H2O/L/s was significantly greater after 200 mg of cromolyn (1.98 ppm) than after 20 mg of cromolyn (0.94 ppm), which was in turn significantly greater than after placebo (0.35 ppm). We then examined whether the greater protection afforded by 200 mg of cromolyn was due to direct inhibition of smooth muscle contraction. We measured the bronchomotor response to the inhalation of serially increasing concentrations of methacholine aerosol (0.06 to 2.0 mg/ml) in 7 asthmatic subjects. Again, each subject was treated on 3 separate days with 200 mg of cromolyn, with 20 mg of cromolyn, and with placebo. We found that methacholine responsiveness was not decreased by either dose of cromolyn. We conclude that cromolyn inhibits sulfur dioxide-induced bronchoconstriction in a dose-dependent manner and that it does not directly inhibit smooth muscle responsiveness.

Adult↗
PubMed1986

The relationship between bronchoalveolar neutrophil recruitment and bronchoconstriction induced by a soluble extract of cotton bracts.

Byssinosis is characterized by an obstructive bronchitis in some workers exposed to cotton dust. Mechanisms of airway alterations induced by cotton dust are unknown. To study mechanisms of these alterations, we administered an aqueous extract of cotton bract (CBE) to normal human subjects. After CBE inhalation, we demonstrated reproducible reductions in flow rates of variable magnitude. The percentage of polymorphonuclear leukocytes (PMN) recovered by bronchoalveolar lavage (BAL) and total PMN per milliliter BAL fluid were increased after challenge with CBE, and these parameters were correlated (r = 0.556 and r = 0.553, respectively) with the degree of bronchoconstriction induced by CBE. In addition, chemotactic factors for PMN were noted in BAL fluid and in supernatant from BAL cell cultures. The degree of BAL fluid chemotactic activity correlated with the degree of bronchoconstriction induced by CBE. Assessment of molecular sieve column effluent demonstrated BAL fluid to have 3 distinct peaks of chemotactic activity (approximate molecular weight, greater than 25,000, 10,000, and less than 1,000 daltons) and cell culture supernatant to contain 1 peak (approximate MW, 10,000 daltons). Complement activation as one source of BAL chemotactic activity was suggested by almost complete inhibition of BAL chemotactic activity after incubation with antibody to the fifth component of complement (C5) and detection of C5a des Arg in BAL fluid from some subjects challenged with CBE. These findings suggest that exposure of volunteer subjects to CBE results in a bronchoalveolar inflammatory response related to both complement activation and chemotactic factor synthesis by luminal cells.

Adult↗
PubMed1987

The role of titratable acidity in acid aerosol-induced bronchoconstriction.

We evaluated the importance of pH, titratable acidity, and specific chemical composition in acid aerosol-induced bronchoconstriction in 8 asthmatic subjects. We administered aerosols of HCl and H2SO4 at pH 2.0 in an unbuffered state and buffered with glycine. The buffered acids were given in order of increasing titratable acidity (defined as the number of ml of 1 N NaOH required to neutralize 100 ml of acid solution to pH 7.0). Each set of buffered or unbuffered acid aerosols was given on a separate day and each aerosol was inhaled through a mouthpiece during 3 min of tidal breathing. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw) before and after inhalation of each aerosol. SRaw increased by more than 50% above baseline in 1 of 8 subjects after inhalation of unbuffered HCl and in no subjects after inhalation of unbuffered H2SO4, even at pH 2.0. In contrast, SRaw increased by greater than 50% in all 8 subjects after inhalation of HCl and glycine at pH 2.0 and 7 of 8 subjects after inhalation of H2SO4 and glycine at pH 2.0. The mean titratable acidity required to increase SRaw by 50% above baseline was calculated for each challenge by linear interpolation; these values for H2SO4 and glycine (5.1 ml of 1 N NaOH) and HCl and glycine (2.2 ml of 1 N NaOH) were slightly, but significantly, different (p = 0.01) and were considerably higher than the titratable acidity of the unbuffered acids at pH 2 (1.0 ml of 1 N NaOH).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

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)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗