TY - JOUR
T1 - A bradykinin-antagonist blocks antigen-induced airway hyperresponsiveness and inflammation in sheep
AU - Solèr, M.
AU - Sielczak, M.
AU - Abraham, W. M.
N1 - Funding Information:
This work was supported by a grant from the Swiss National Science Foundation, Swiss Society for Pneumology and NIH-HL 33897 .
PY - 1990
Y1 - 1990
N2 - The effects of a new bradykinin-antagonist, NPC-567 (D-Arg {hydroxyproline3, D-phenylalanine7} bradykinin) were studied on antigen-induced airway hyperresponsiveness and inflammation in allergic sheep (n = 7). Specific lung resistance (sRL) was used to assess airway responses to inhaled Ascaris suum-antigen. Airway responsiveness was determined from slopes of cumulative dose-response-curves (DRC) to inhaled carbachol. DRCs were performed at baseline and 2 h after an inhalation challenge with antigen. Bronchoalveolar lavage, performed before antigen-challenge and after the post-challenge DRC was used to assess antigen-induced inflammatory changes. For these studies NPC-567 was given as an aerosol (20 breaths, 10 mg/ml) 30 min before antigen challenge and (400 breaths, 2 mg/ml) co-administered with the Ascaris suum antigen. The immediate increase in specific lung resistance (sRL) after antigen challenge was not different with (232 ± 152% increase) or without drug pre-treatment (148 ± 129% increase). In the control trial, antigen challenge led to an increase in slope of the post-challenge DRC by 123 ± 118% compared to baseline (p < 0.05). This hyperresponsiveness was almost completely prevented by NPC-567 (increase in slope 32 ± 64%, p < 0.05 vs. control). Similarly, the antigen-induced inflammatory response, characterized by a significant 3.3-fold increase over baseline in the percentage of neutrophils in the control-experiment, was blocked by the bradykinin-antagonist. These results suggest that bradykinin may be involved in the pathogenesis of antigen-induced airway inflammation and the consequent development of airway hyperresponsiveness in sheep.
AB - The effects of a new bradykinin-antagonist, NPC-567 (D-Arg {hydroxyproline3, D-phenylalanine7} bradykinin) were studied on antigen-induced airway hyperresponsiveness and inflammation in allergic sheep (n = 7). Specific lung resistance (sRL) was used to assess airway responses to inhaled Ascaris suum-antigen. Airway responsiveness was determined from slopes of cumulative dose-response-curves (DRC) to inhaled carbachol. DRCs were performed at baseline and 2 h after an inhalation challenge with antigen. Bronchoalveolar lavage, performed before antigen-challenge and after the post-challenge DRC was used to assess antigen-induced inflammatory changes. For these studies NPC-567 was given as an aerosol (20 breaths, 10 mg/ml) 30 min before antigen challenge and (400 breaths, 2 mg/ml) co-administered with the Ascaris suum antigen. The immediate increase in specific lung resistance (sRL) after antigen challenge was not different with (232 ± 152% increase) or without drug pre-treatment (148 ± 129% increase). In the control trial, antigen challenge led to an increase in slope of the post-challenge DRC by 123 ± 118% compared to baseline (p < 0.05). This hyperresponsiveness was almost completely prevented by NPC-567 (increase in slope 32 ± 64%, p < 0.05 vs. control). Similarly, the antigen-induced inflammatory response, characterized by a significant 3.3-fold increase over baseline in the percentage of neutrophils in the control-experiment, was blocked by the bradykinin-antagonist. These results suggest that bradykinin may be involved in the pathogenesis of antigen-induced airway inflammation and the consequent development of airway hyperresponsiveness in sheep.
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U2 - 10.1016/0952-0600(90)90003-2
DO - 10.1016/0952-0600(90)90003-2
M3 - Article
C2 - 2135209
AN - SCOPUS:0025360685
VL - 3
SP - 9
EP - 15
JO - Pulmonary Pharmacology and Therapeutics
JF - Pulmonary Pharmacology and Therapeutics
SN - 1094-5539
IS - 1
ER -