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Bradykinin-induced release of thromboxane B2 into bronchoalveolar lavage fluid of guinea pigs: relationship to airflow obstruction

Kawikova, Ivana; Arakawa, Hirokazu; Petersson, Maud; Löfdahl, Claes-Göran LU ; Skoogh, Bengt-Eric and Lotvall, Jan (1995) In European Journal of Pharmacology 280(3). p.293-299
Abstract
The aim of this study was to evaluate the role of thromboxane A2 in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was determined by radioimmunoassay. The animals were pretreated with propranolol (1 mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration. Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2 release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in sham). A thromboxane synthase... (More)
The aim of this study was to evaluate the role of thromboxane A2 in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was determined by radioimmunoassay. The animals were pretreated with propranolol (1 mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration. Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2 release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in sham). A thromboxane synthase inhibitor (OKY-046, 30 mg/kg i.v.; ((E-E)-3-[p(1H-imidazole-1-yl-methyl) phenyl]-2-propenoic acid hydrochloride mono-hydrate)) or a thromboxane A2 receptor antagonist (ICI192,605, 0.5 mg/kg i.v.; (4-(Z)-6-(2-o-chloro-phenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid)) reduced the Pi increase evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O, respectively). OKY-046 abolished the thromboxane B2 release. A platelet-activating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4-(chlorophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diazepin-2-yl]1-4-(4-morpholinyl)-1-propanon) did not significantly affect any measured parameter. We conclude that, in guinea pigs, bradykinin-induced airway effects are associated with a local thromboxane A2 release. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Bradykinin, Thromboxane, Airflow obstruction, WEB2086, ICI192, 605, OKY-046
in
European Journal of Pharmacology
volume
280
issue
3
pages
293 - 299
publisher
Elsevier
external identifiers
  • pmid:8566097
  • scopus:0029033901
ISSN
1879-0712
DOI
10.1016/0014-2999(95)00207-2
language
English
LU publication?
yes
id
c56ed603-6f7b-4b2a-8d51-7bb6d06db1a5 (old id 1109402)
date added to LUP
2008-07-28 14:06:30
date last changed
2017-01-01 04:31:43
@article{c56ed603-6f7b-4b2a-8d51-7bb6d06db1a5,
  abstract     = {The aim of this study was to evaluate the role of thromboxane A2 in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was determined by radioimmunoassay. The animals were pretreated with propranolol (1 mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration. Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2 release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in sham). A thromboxane synthase inhibitor (OKY-046, 30 mg/kg i.v.; ((E-E)-3-[p(1H-imidazole-1-yl-methyl) phenyl]-2-propenoic acid hydrochloride mono-hydrate)) or a thromboxane A2 receptor antagonist (ICI192,605, 0.5 mg/kg i.v.; (4-(Z)-6-(2-o-chloro-phenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid)) reduced the Pi increase evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O, respectively). OKY-046 abolished the thromboxane B2 release. A platelet-activating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4-(chlorophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diazepin-2-yl]1-4-(4-morpholinyl)-1-propanon) did not significantly affect any measured parameter. We conclude that, in guinea pigs, bradykinin-induced airway effects are associated with a local thromboxane A2 release.},
  author       = {Kawikova, Ivana and Arakawa, Hirokazu and Petersson, Maud and Löfdahl, Claes-Göran and Skoogh, Bengt-Eric and Lotvall, Jan},
  issn         = {1879-0712},
  keyword      = {Bradykinin,Thromboxane,Airflow obstruction,WEB2086,ICI192,605,OKY-046},
  language     = {eng},
  number       = {3},
  pages        = {293--299},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Bradykinin-induced release of thromboxane B2 into bronchoalveolar lavage fluid of guinea pigs: relationship to airflow obstruction},
  url          = {http://dx.doi.org/10.1016/0014-2999(95)00207-2},
  volume       = {280},
  year         = {1995},
}