title: Effects of three alpha 2-adrenoceptor agonists, rilmenidine, UK 14304 and clonidine on bradykinin- and substance P-induced airway microvascular leakage in guinea-pigs.
abstract: The effects of three alpha 2-adrenoceptor agonists, clonidine, rilmenidine and UK 14304 on the increase of microvascular permeability induced by bradykinin or substance P in guinea-pigs airways have been studied in vivo. Extravasation of intravenously (i.v.) injected Evans blue dye was used as index of permeability. The effects of the three alpha 2-adrenoceptor agonists on the contraction induced by bradykinin (0.3 micrograms.kg-1, i.v.) and substance P (0.3 micrograms.kg-1, i.v.) were also studied on the isolated guinea-pig trachea. The increase of plasma exudation induced by bradykinin (0.3 micrograms.kg-1, i.v.) was inhibited partially by rilmenidine and UK 14304 (20 micrograms and 100 micrograms, intratracheally) respectively. These two substances had no action on the effects of substance P. The effects of rilmenidine and UK 14304 were abolished by alpha 2-blockers (idazoxan 1mg.kg-1 i.v. and RX 821001 100 micrograms.kg-1, i.v.), but they were not altered by the alpha 1-blocker prazosin (30 micrograms.kg-1, i.v.). Under similar conditions, clonidine or the alpha 1-adrenoceptor agonist methoxamine were without significant effects. In vitro, rilmenidine and UK 14304 inhibited partially the contractile effects of bradykinin but not those of substance P. To conclude, both rilmenidine and UK 14304 inhibit the bradykinin-induced increase of vascular permeability in the airways, and they probably do so on peptidergic nerve endings at the prejunctional level since these substances are without effect on substance P. The absence of activity of clonidine in our study might be due to a difference in spectrum of action on the several types of alpha 2-adrenergic or imidazole receptors.
authors.affiliation: Faculté de Médecine Paris-Ouest, Laboratoire de Pharmacologie, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Biyah
authors.forename: C
authors.initials: C
authors.lastname: Advenier
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D000068438:Brimonidine Tartrate; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D015633:Extravascular Lung Water / Q000187:drug effects; D006168:Guinea Pigs; D019329:Idazoxan / Q000031:analogs & derivatives; D010080:Oxazoles / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D000077769:Rilmenidine; D013373:Substance P / Q000494:pharmacology*; D014132:Trachea / Q000098:blood supply
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D004146:Dioxanes; D010080:Oxazoles; D011810:Quinoxalines; D013373:Substance P; D000068438:Brimonidine Tartrate; C058525:2-methoxyidazoxan; D003000:Clonidine; D000109:Acetylcholine; D000077769:Rilmenidine; D001920:Bradykinin; D011224:Prazosin; D019329:Idazoxan