title: Bradykinin and changes in microvascular permeability in the hamster cheek pouch: role of nitric oxide.
abstract: 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 dextranfluorescein isothiocyanate (FITC-dextran) extravasation. 2. Bradykinin superfusion (but not [des-Arg9]-bradykinin up to 3 x 10(-6) M) induced an increase in microvascular permeability (log EC50: -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 B2 receptor antagonist (estimated log ID50: -9.5 +/- 0.2). 3. The effects of bradykinin (3 x 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 A2 (U46619, 3 x 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 B2 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.
authors.affiliation: Départment de Pneumologie, Institut de Recherches Servier, Suresnes, France.
authors.forename: M
authors.initials: M
authors.lastname: Félétou
authors.forename: E
authors.initials: E
authors.lastname: Bonnardel
authors.forename: E
authors.initials: E
authors.lastname: Canet
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002196:Capillaries / Q000033:anatomy & histology / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D018002:Receptors, Bradykinin / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018002:Receptors, Bradykinin; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C065679:icatibant; D019001:Nitric Oxide Synthase; D001920:Bradykinin