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Bradykinin and changes in microvascular permeability in the hamster cheek pouch: role of nitric oxide
Author(s) -
Félétou M.,
Bonnardel E.,
Canet E.
Publication year - 1996
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.1476-5381.1996.tb15547.x
Subject(s) - cheek pouch , bradykinin , chemistry , cromakalim , extravasation , sodium nitroprusside , nitric oxide , medicine , vasodilation , endocrinology , vasoconstriction , pharmacology , hamster , agonist , biochemistry , receptor , immunology
1 The objective of this study in the hamster cheek pouch was to investigate the role of nitric oxide in bradykinin‐induced microvascular leakage. The cheek pouch microcirculatory bed of the anaesthetized hamster was directly observed under microscope and vascular leakage was evidenced by dextran‐fluorescein isothiocyanate (FITC‐dextran) extravasation. 2 Bradykinin superfusion (but not [des‐Arg 9 ]‐bradykinin up to 3 × 10 −6 m ) induced an increase in microvascular permeability (log EC 50 : −6.5 ± 0.4) which was exclusively located on the post‐capillary venule. Plasma extravasation was blocked by intravenous pretreatment with Hoe 140, a bradykinin B 2 receptor antagonist (estimated log ID 50 : −9.5 ± 0.2). 3 The effects of bradykinin (3 × 10 −7 m ) superfusion were partially but significantly inhibited by indomethacin (10 −5 m , P < 0.05) and abolished by pretreatment with L‐nitro‐arginine (L‐NOARG; 10 −5 m ). 4 Acetylcholine (10 −6 m , which releases endothelial nitric oxide (NO)) and sodium nitroprusside (10 −6 m , a nitrovasodilator) superfusion did not induce any changes in permeability, per se . Cromakalim (10 −5 m , a potassium channel opener) superfusion induced a moderate but significant plasma extravasation. 5 The effects of bradykinin, blocked by L‐NOARG pretreatment, were restored by the co‐perfusion of either sodium nitroprusside or cromakalim. Conversely vasoconstriction, produced by a stable analogue of thromboxane A 2 (U46619, 3 × 10 −7 m ), inhibited the increase in permeability produced by bradykinin. 6 The measurement of arteriolar diameter showed that bradykinin induced a vasodilatation which was blocked by L‐NOARG. L‐NOARG in itself was a powerful vasoconstrictor. Sodium nitroprusside and cromakalim, in the presence of L‐NOARG, were able to restore the inhibited vasodilator response to bradykinin. 7 These results suggest: (1) bradykinin‐induced microvascular leakage is mediated by bradykinin B 2 receptor activation; (2) the increase in permeability is due to two different independent phenomena, i.e. post‐capillary venular endothelial gap formation and arteriolar vasodilatation which increases the post‐capillary venular transmural pressure; (3) NO is only involved in the arteriolar dilatation component of the bradykinin‐induced increase in microvascular permeability.