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Bradykinin-induced airflow obstruction and airway plasma exudation: effects of drugs that inhibit acetylcholine, thromboxane A2 or leukotrienes

Kawikova, Ivana; Arakawa, Hirokazu; Löfdahl, Claes-Göran LU ; Skoogh, Bengt-Eric and Lotvall, Jan (1993) In British Journal of Pharmacology 110(2). p.657-664
Abstract
1 The mechanisms behind bradykinin-induced effects in the airways are considered to be largely indirect. The role of cholinergic nerves and eicosanoids, and their relationship in these mechanisms were investigated in guinea-pigs.

2 The role of cholinergic nerves was studied in animals given atropine (1 mg kg-', i.v.), hexamethonium

(2 mg kg-', i.v.), or vagotomized. To study the role of eicosanoids, animals were pretreated with a thromboxane A2 (TxA2) receptor antagonist (ICI 192,605; 106 mol kg-', i.v.) or with a leukotriene (LT) receptor C4/D4/E4 antagonist (ICI 198,615; 106 mol kg-', i.v.).

3 After pretreatment with a drug, bradykinin (150 nmol) was instilled into the tracheal lumen. We measured both airway... (More)
1 The mechanisms behind bradykinin-induced effects in the airways are considered to be largely indirect. The role of cholinergic nerves and eicosanoids, and their relationship in these mechanisms were investigated in guinea-pigs.

2 The role of cholinergic nerves was studied in animals given atropine (1 mg kg-', i.v.), hexamethonium

(2 mg kg-', i.v.), or vagotomized. To study the role of eicosanoids, animals were pretreated with a thromboxane A2 (TxA2) receptor antagonist (ICI 192,605; 106 mol kg-', i.v.) or with a leukotriene (LT) receptor C4/D4/E4 antagonist (ICI 198,615; 106 mol kg-', i.v.).

3 After pretreatment with a drug, bradykinin (150 nmol) was instilled into the tracheal lumen. We measured both airway insufflation pressure (Pi), to assess airway narrowing, and the content of Evans blue dye in airway tissue, to assess plasma exudation.

4 Bradykinin instillation into the trachea caused an increase in Pi and extravasation of Evans blue dye.

The increase in Pi was significantly attenuated by atropine or the TxA2 receptor antagonist, but not by hexamethonium, vagotomy or the LT receptor antagonist.

5 The bradykinin-induced exudation of Evans blue dye was significantly attenuated in the intrapulmonary

airways by the TxA2 receptor antagonist, but not by atropine, hexamethonium, cervical vagotomy or the LT receptor antagonist.

6 A thromboxane-mimetic, U-46619 (20 nmol kg-', i.v. or 10 nmol intratracheally), caused both an increase in Pi and extravasation of Evans blue dye at all airway levels. Atropine pretreatment slightly attenuated the peak Pi after the intratracheal administration of U-46619, but not after i.v. administration.

7 We conclude that peripheral cholinergic nerves are involved in bradykinin-induced airflow obstruction

but not plasma exudation, and that TxA2 is involved in both airflow obstruction and airway plasma exudation induced by bradykinin given via the airway route. TxA2-induced airflow obstruction is mediated only to a minor degree, via the release of acetylcholine in the airways. (Less)
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author
publishing date
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Contribution to journal
publication status
published
subject
keywords
bronchoconstriction, Asthma, airway oedema, inflammation, plasma exudation, cholinergic nerves, bradykinin, thromboxane, leukotrienes
in
British Journal of Pharmacology
volume
110
issue
2
pages
657 - 664
publisher
The British Pharmacological Society
external identifiers
  • pmid:8242239
  • scopus:0027219047
ISSN
1476-5381
language
English
LU publication?
no
id
99a21d3a-a41f-476a-b0f9-481afd225c92 (old id 1107391)
alternative location
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2175931
date added to LUP
2008-07-30 17:14:38
date last changed
2017-01-01 06:45:31
@article{99a21d3a-a41f-476a-b0f9-481afd225c92,
  abstract     = {1 The mechanisms behind bradykinin-induced effects in the airways are considered to be largely indirect. The role of cholinergic nerves and eicosanoids, and their relationship in these mechanisms were investigated in guinea-pigs.<br/><br>
2 The role of cholinergic nerves was studied in animals given atropine (1 mg kg-', i.v.), hexamethonium<br/><br>
(2 mg kg-', i.v.), or vagotomized. To study the role of eicosanoids, animals were pretreated with a thromboxane A2 (TxA2) receptor antagonist (ICI 192,605; 106 mol kg-', i.v.) or with a leukotriene (LT) receptor C4/D4/E4 antagonist (ICI 198,615; 106 mol kg-', i.v.).<br/><br>
3 After pretreatment with a drug, bradykinin (150 nmol) was instilled into the tracheal lumen. We measured both airway insufflation pressure (Pi), to assess airway narrowing, and the content of Evans blue dye in airway tissue, to assess plasma exudation.<br/><br>
4 Bradykinin instillation into the trachea caused an increase in Pi and extravasation of Evans blue dye.<br/><br>
The increase in Pi was significantly attenuated by atropine or the TxA2 receptor antagonist, but not by hexamethonium, vagotomy or the LT receptor antagonist.<br/><br>
5 The bradykinin-induced exudation of Evans blue dye was significantly attenuated in the intrapulmonary<br/><br>
airways by the TxA2 receptor antagonist, but not by atropine, hexamethonium, cervical vagotomy or the LT receptor antagonist.<br/><br>
6 A thromboxane-mimetic, U-46619 (20 nmol kg-', i.v. or 10 nmol intratracheally), caused both an increase in Pi and extravasation of Evans blue dye at all airway levels. Atropine pretreatment slightly attenuated the peak Pi after the intratracheal administration of U-46619, but not after i.v. administration.<br/><br>
7 We conclude that peripheral cholinergic nerves are involved in bradykinin-induced airflow obstruction<br/><br>
but not plasma exudation, and that TxA2 is involved in both airflow obstruction and airway plasma exudation induced by bradykinin given via the airway route. TxA2-induced airflow obstruction is mediated only to a minor degree, via the release of acetylcholine in the airways.},
  author       = {Kawikova, Ivana and Arakawa, Hirokazu and Löfdahl, Claes-Göran and Skoogh, Bengt-Eric and Lotvall, Jan},
  issn         = {1476-5381},
  keyword      = {bronchoconstriction,Asthma,airway oedema,inflammation,plasma exudation,cholinergic nerves,bradykinin,thromboxane,leukotrienes},
  language     = {eng},
  number       = {2},
  pages        = {657--664},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Bradykinin-induced airflow obstruction and airway plasma exudation: effects of drugs that inhibit acetylcholine, thromboxane A2 or leukotrienes},
  volume       = {110},
  year         = {1993},
}