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Evidence for reduction of bradykinin‐induced bronchoconstriction in guinea‐pigs by release of nitric oxide
Author(s) -
Ricciardolo Fabio L.M.,
Nadel Jay A.,
Yoishihara Shigemi,
Geppetti Pierangelo
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17117.x
Subject(s) - bronchoconstriction , bradykinin , nitric oxide , guinea pig , pharmacology , chemistry , nitric oxide synthase , medicine , anesthesia , asthma , receptor
1 In this study the influence of nitric oxide (NO) on the bronchoconstriction induced by bradykinin in anaesthetized and artifically ventilated guinea‐pigs pretreated with atropine was investigated. 2 Aerosol administration of bradykinin (0.1 −1 m m , 40 breaths) caused a dose‐dependent increase in lung resistance (R 1 ): maximum increase in R 1 was 2.5 fold the baseline value. Pretreatment with aerosolized N G ‐nitro‐ 1 ‐arginine methyl ester ( 1 ‐NAME) or N G ‐monomethyl‐ 1 ‐arginine ( 1 ‐NMMA) (1 m m , 10 breaths every 5min for 30min), NO synthase inhibitors, markedly increased the bron‐choconstrictor response to bradykinin. 1 ‐Arginine, but not D‐arginine, (3 m m , 10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to aerosolized bradykinin caused by 1 ‐NAME and 1 ‐NMMA. 3 1 ‐NAME (1 m m , 10 breaths every 5 min for 30 min) increased the bronchoconstriction induced by intravenous bradykinin (1‐10nmol kg 1 ). 1 ‐Arginine, but not D‐arginine, (10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to intravenous bradykinin caused by 1 ‐NAME. 4 The increase in R L induced by capsaicin, either aerosol (10 μ m , 10 breaths) or i.v. (20 nmol kg −1 ) was not affected by 1 ‐NAME (1 m m , 10 breaths every 5 min for 30 min). Acute resection of the vagi did not affect the bronchoconstriction evoked by bradykinin in guinea‐pigs, either in the absence or presence of 1 ‐NAME (1 m m , 10 breaths every 5 min for 30 min). 4 These results suggest that, irrespective of the route of administration, bradykinin releases NO or a related molecule which exerts a bronchodilator action that opposes the bronchoconstrictor mechanisms activated by bradykinin itself.