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Airway hyperresponsiveness to bradykinin induced by allergen challenge in actively sensitised Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature15208
Source
Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):166-78
Publication Type
Article
Date
Feb-2004
Author
K M Ellis
C. Cannet
L. Mazzoni
J R Fozard
Author Affiliation
Research Department, Novartis Institute for Biomedical Research, 4002 Basel, Switzerland.
Source
Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):166-78
Date
Feb-2004
Language
English
Publication Type
Article
Keywords
Adenosine - pharmacology
Animals
Arachidonate 5-Lipoxygenase - physiology
Bradykinin - pharmacology - physiology
Bronchial Hyperreactivity - immunology - physiopathology
Bronchoconstriction - drug effects
Bronchoconstrictor Agents - pharmacology
Comparative Study
Disease Models, Animal
Endopeptidases - physiology
Lung - pathology
Male
Mast Cells - physiology
Methacholine Chloride - pharmacology
Ovalbumin - immunology
Rats
Rats, Inbred BN
Receptors, Adrenergic, beta-1 - agonists
Receptors, Adrenergic, beta-2 - antagonists & inhibitors
Receptors, Muscarinic - physiology
Tachykinins - physiology
Abstract
The mechanism(s) of bradykinin-induced bronchoconstriction was investigated in the Brown Norway (BN) rat model of allergic asthma. Bronchoconstrictor responses to i.v. bradykinin in BN rats were maximally augmented 24 h following challenge with allergen and declined at later time points. Histological evaluation of the inflammatory status of the lungs after ovalbumin (OA) challenge showed a marked inflammatory response, which was maximal at 24 h and declined thereafter. However, pretreatment with budesonide did not inhibit the augmented bronchoconstrictor response to bradykinin 24 h after allergen challenge. The selective B1 receptor agonist, Lys-[desArg9]-BK had no bronchoconstrictor effects, whereas the selective B2 receptor antagonist, HOE 140, abolished the response to bradykinin in OA-challenged animals. The augmented response to bradykinin was not affected by methysergide, indomethacin, disodium cromoglycate, iralukast, the 5-lipoxygenase inhibitor, CGS8515, or the NK2 receptor antagonist, SR48968. It was, however, partially inhibited by atropine both in saline- and OA-challenged animals. Pretreatment with captopril and thiorphan markedly potentiated responses to bradykinin both in saline- and OA-challenged animals. Thus, augmentation of the bronchoconstrictor response to bradykinin occurs in actively sensitised BN rats 24 h after challenge with OA and is associated with marked pulmonary inflammation. The response is entirely B2 receptor mediated and approximately 50% of the response is cholinergic. However, mast cell activation, the products of the cyclooxygenase or 5-lipoxygenase pathways and tachykinins are not involved. Peptidase inhibition mimics the effect of allergen challenge on the bronchoconstrictor response to bradykinin and it remains possible that the mechanism of the augmented response to bradykinin following allergen challenge involves downregulation of peptidase activity as a consequence of the inflammatory response.
PubMed ID
14727005 View in PubMed
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The effects of a 5-lipoxygenase inhibitor on acute mountain sickness and urinary leukotriene e4 after ascent to high altitude.

https://arctichealth.org/en/permalink/ahliterature176217
Source
Chest. 2005 Feb;127(2):565-70
Publication Type
Article
Date
Feb-2005
Author
Colin K Grissom
Lori D Richer
Mark R Elstad
Author Affiliation
Pulmonary Division, LDS Hospital, Eighth Ave and C St, Salt Lake City, UT 84143, USA. LDCGRISS@ihc.com
Source
Chest. 2005 Feb;127(2):565-70
Date
Feb-2005
Language
English
Publication Type
Article
Keywords
Acclimatization - drug effects - physiology
Administration, Oral
Adult
Alaska
Altitude Sickness - physiopathology - prevention & control
Arachidonate 5-Lipoxygenase - physiology
Double-Blind Method
Drug Administration Schedule
Female
Humans
Hydroxyurea - adverse effects - analogs & derivatives - therapeutic use
Inflammation Mediators - blood
Leukotriene E4 - urine
Lipoxygenase Inhibitors - adverse effects - therapeutic use
Male
Middle Aged
Mountaineering - physiology
Oximetry
Premedication
Statistics as Topic
Treatment Outcome
Abstract
Elevated urine and blood leukotriene levels have been reported after ascent to high altitude in association with acute mountain sickness (AMS) and high-altitude pulmonary edema. Zileuton is an inhibitor of the enzyme 5-lipoxygenase that catalyzes conversion of arachidonic acid to leukotrienes. Study objectives and design: The objectives of this randomized, double-blind, placebo-controlled clinical trial were to determine whether zileuton (600 mg po qid) is effective prophylaxis for AMS, and to measure the effect of ascent to high altitude and zileuton on urinary leukotriene E(4) levels.
The study group consisted of volunteers from among climbers on the West Buttress of Mt. McKinley (Denali), Alaska. After baseline urine samples at sea level, subjects flew by airplane to 2,300 m, and then ascended to the 4,200-m camp in 5 to 10 days.
Using an enzyme immunoassay, urinary leukotriene E(4) was found to decrease after ascent to high altitude in both the zileuton and placebo groups. Urinary leukotriene E(4) in the zileuton group (n = 9) decreased from 67 +/- 35 pg/mg creatinine at sea level to 33 +/- 22 pg/mg creatinine at high altitude (p = 0.003) [mean +/- SD]. Urinary leukotriene E(4) in the placebo group (n = 9) decreased from 97 +/- 82 pg/mg creatinine at sea level to 44 +/- 21 pg/mg creatinine at high altitude (p = 0.045). One subject in the zileuton group and three subjects in the placebo group met Lake Louise criteria for AMS after arriving at 4,200 m (p = 0.257).
Elevated leukotrienes are not associated with ascent to high altitude. In subjects with AMS, urinary leukotrienes were not elevated, suggesting that leukotrienes may not be a component of the pathophysiology of AMS. The low incidence of AMS and the small sample size in this study prevented determination of whether zileuton is effective prophylaxis for AMS.
PubMed ID
15705997 View in PubMed
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Involvement of cysteinyl leukotrienes in airway smooth muscle cell DNA synthesis after repeated allergen exposure in sensitized Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature15646
Source
Br J Pharmacol. 1999 Jul;127(5):1151-8
Publication Type
Article
Date
Jul-1999
Author
M. Salmon
D A Walsh
T J Huang
P J Barnes
T B Leonard
D W Hay
K F Chung
Author Affiliation
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
Source
Br J Pharmacol. 1999 Jul;127(5):1151-8
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Allergens - immunology
Animals
Arachidonate 5-Lipoxygenase - physiology
Bronchi - drug effects - metabolism
Cell Count
Cysteine - physiology
DNA - biosynthesis
Eosinophils - physiology
Leukotrienes - physiology
Male
Muscle, Smooth - metabolism
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
Airway smooth muscle thickening is a characteristic feature of airway wall remodelling in chronic asthma. We have investigated the role of the leukotrienes in airway smooth muscle (ASM) and epithelial cell DNA synthesis and ASM thickening following repeated allergen exposure in Brown Norway rats sensitized to ovalbumin. There was a 3 fold increase in ASM cell DNA synthesis, as measured by percentage bromodeoxyuridine (BrdU) incorporation, in repeatedly ovalbumin-exposed (4.1%, 3.6-4.6; mean, 95% c.i.) compared to chronically saline-exposed rats (1.3%, 0.6-2.1; P
PubMed ID
10455261 View in PubMed
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