The effects of a kinin antagonist on changes in lung function and plasma extravasation into the airways following challenge of sensitized guinea-pigs.
BACKGROUND
It has been suggested that kinins may play a role in allergic pathophysiology of the airways, contributing to bronchoconstriction and oedema formation. Raised levels of kinin generating enzymes and kinins are found in the airways during allergic responses.


OBJECTIVE
Using an in vivo animal model of allergen induced increase in airways resistance we investigated the effects of the bradykinin antagonist Hoe 140, in order to assess the possible contribution of kinins to this response.


METHODS
Guinea-pigs were sensitized and challenged with ovalbumin (OA) or saline via the endotracheal route and the resulting increase in airways resistance was measured by whole body plethysmography. At 240 min after challenge, bronchoalveolar lavage fluid (BALF) was taken and albumin content and kallikrein-like activity determined by rocket immunoelectrophoresis and use of artificial substrates respectively. Pretreatment of animals with the bradykinin antagonist Hoe 140 at 6.7, 20 or 66.7 nmol/kg or aprotinin (46,000 kallikrein inhibitor units/kg) was by i.p. injection 10 min before challenge.


RESULTS
Pre-treatment with Hoe 140 dose dependently attenuated the increase in airways resistance following allergen challenge. Kallikrein-like activity and albumin in BALF were unaltered. Aprotinin reduced the kallikrein-like activity in BALF but did not alter airways resistance.


CONCLUSIONS
Kinins may contribute to a significant part of allergen-induced airways resistance increase in this model but not via an effect on plasma extravasation.
Featherstone
R L
RL
Clinical Pharmacology, Southampton General Hospital, UK.
Parry
J E
JE
Church
M K
MK
D000403:Airway Resistance / Q000187:drug effects; D000418:Albumins / Q000032:analysis*; D000707:Anaphylaxis / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010047:Ovalbumin; D010539:Permeability
D000418:Albumins; C065679:icatibant; D010047:Ovalbumin; D007611:Aprotinin; D001920:Bradykinin