ABSTRACT
It has been reported that several bronchoconstrictors generate nitric oxide (NO), counteracting bronchoconstriction, and removal of bronchial epithelia reduces NO production. However, it has not been elucidated whether neurokinin A (NKA), a potent bronchoconstrictor liberated from nerve terminals, generates NO. Specific questions in this study were (1) does NKA also generate NO, (2) does NO counteract NKA-induced bronchoconstriction, and (3) does the NO generation require bronchial epithelial cells? In an in vivo study exogenous as well as endogenous (capsaicin-induced) NKA increased airway opening pressure (P(ao)) and the exhaled NO level, and both were inhibited by an antagonist selective for NK(2) receptor (a receptor for NKA), SR48968. The exhaled NO level became negligible with an inhibitor of NO synthase (NOS) type 1-3 (N(G)-nitro-L-arginine methyl ester, L-NAME) with increased P(ao), but not with a NOS type 2 inhibitor. In an in vitro study, NKA increased the nitrite/nitrate level in superfused fluid of tracheal segments. Removing smooth muscle reduced nitrite/nitrate in the fluid to negligible levels, while the level was unchanged with removal of the epithelia. Pretreatment with l-NAME enhanced the tension of epithelia-removed tracheal segments. These findings indicate that (1) NKA generates NO, (2) NO counteracts NKA-induced bronchoconstriction, and (3) NKA activates NOS in the muscle layer, independently of bronchial epithelia.
Subject(s)
Bronchoconstriction/drug effects , Muscle, Smooth/drug effects , Neurokinin A/pharmacology , Nitric Oxide/biosynthesis , Airway Resistance/drug effects , Animals , Benzamides/pharmacology , Capsaicin/pharmacology , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Epithelial Cells/physiology , Guanidines/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Muscle, Smooth/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Nitrates/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type I , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Nitrites/metabolism , Piperidines/pharmacology , Receptors, Neurokinin-2/agonists , Receptors, Neurokinin-2/antagonists & inhibitors , Trachea/physiologyABSTRACT
In previous studies the exhaled nitric oxide (NO) level of asthma patients was investigated only in association with bronchial inflammation, and whether the degree of bronchoconstriction itself influences the exhaled NO level has never been investigated. We therefore evaluated the effect of inhalation of a bronchoconstrictor (methacholine) or a bronchodilator (salbutamol) on the exhaled NO level of healthy volunteers and asthma patients. The exhaled NO level of the healthy volunteers decreased after methacholine inhalation. The exhaled NO level of patients with mild or moderate persistent asthma, who had no asthma attacks on the day of measurement, increased after salbutamol inhalation, and the exhaled NO level of asthma patients during asthma attacks increased after salbutamol inhalation followed by intravenous drip infusion of aminophylline. It is suspected that large amounts of NO are trapped in the lung distal to the constricted airway, contributing little to the exhaled NO level at the mouth. However, we expect that the trapped NO is exhaled at a larger fraction after the dilatation of the constricted small airway, thereby increasing the exhaled NO level at the mouth. In conclusion, the results of this study suggest that acute changes in bronchoconstriction themselves influence the exhaled NO level independently of the change in NO synthase activity associated with airway inflammation.
Subject(s)
Asthma/physiopathology , Bronchoconstriction/physiology , Nitric Oxide/analysis , Adult , Albuterol/pharmacology , Breath Tests , Bronchoconstrictor Agents/pharmacology , Bronchodilator Agents/pharmacology , Humans , Male , Methacholine Chloride/pharmacology , Nitric Oxide/metabolism , RespirationABSTRACT
We studied adenosine deaminase (ADA) activity in bronchoalveolar lavage fluid (BALF) specimens from 24 patients with sarcoidosis. Mean BALF-ADA activity was significantly (p < 0.0001) elevated in patients with sarcoidosis (1.02 +/- 1.01 IU/L, mean +/- SD) compared to the subjects in a healthy control group (0.08 +/- 0.29 IU/L). In the sarcoidosis patients with high BALF-ADA activity (> or = 1.0 IU/L), AaDO2 was significantly (p < 0.0001) elevated compared to its level in patients with normal BALF-ADA activity (< 1.0 IU/L). BALF-ADA activity was significantly (p < 0.01) higher in patients who exhibited lung-field accumulations on 67Ga scintigrams compared to those with no accumulations, and significantly (p < 0.001) higher in patients undergoing corticosteroid treatment compared to in those patients who did not receive such treatment. These findings were similar to the results of studies using data on BALF-ADA/albumin ratios. Furthermore, they suggest that the localized production of ADA may increase in sarcoidosis patients displaying 67Ga scintigram lung-field accumulations with increased AaDO2, and that BALF-ADA activity may be a useful indicator of disease activity and the need for treatment.
Subject(s)
Adenosine Deaminase/analysis , Bronchoalveolar Lavage Fluid/chemistry , Sarcoidosis, Pulmonary/diagnosis , Adult , Biomarkers/analysis , Female , Humans , Male , Middle AgedABSTRACT
Bronchiolitis obliterans organizing pneumonia (BOOP) occurred in a 53-year-old woman with well-documented Sjögren's syndrome (SjS) and polymyositis (PM). BOOP has often been reported as a pulmonary manifestation of collagen vascular diseases, mainly rheumatoid arthritis (RA), but the association of BOOP and PM has rarely been documented. A search of the literature showed only 16 case reports of BOOP associated with polymyositis-dermatomyositis (PM-DM). It is interesting that BOOP occurred prior to PM-DM, while it is commonly believed to occur after RA.
