title: Evidence that epithelium-dependent relaxation of vascular smooth muscle detected by co-axial bioassays is not attributable to hypoxia.
abstract: 1. The present study was undertaken to examine further the contribution of hypoxia to airway epithelium-dependent relaxation of rat aorta in the co-axial bioassay. 2. Endothelium-denuded rat aorta contracted with phenylephrine (0.05 microM) relaxed in a time-dependent manner (t1/2 = 8.3 +/- 0.4 min, n = 38) when the bathing solution was bubbled with 95% N2 and 5% CO2. In co-axial bioassays, the t1/2 for histamine (100 microM; guinea-pig trachea)- and methacholine (100 microM; rabbit bronchus)- induced relaxation was 1.9 +/- 0.2 min (n = 14) and 1.2 +/- 0.1 min (n = 26), respectively. 3. Hypoxia-induced relaxation was not associated with a rise in intracellular guanosine 3':5'-cyclic monophosphate (cyclic GMP). This contrasts with previous findings of an elevation in cyclic GMP associated with epithelium-dependent relaxation of rat aorta in co-axial bioassays. 4. Hypoxia-induced vascular relaxation was antagonized by the ATP-sensitive K+ channel blocker, glibenclamide (100 microM). In contrast, glibenclamide (100 microM) failed to inhibit histamine (100 microM; guinea-pig trachea)- and methacholine (0.1-100 microM; rabbit bronchus)-induced release of epithelium-derived inhibitory factor (EpDIF), in co-axial bioassays. Glibenclamide (100 microM) antagonized BRL 38227 (lemakalin), but not isoprenaline-induced relaxation of phenylephrine-contracted rat aorta. 5. These data strongly suggest that the airway epithelium-dependent relaxant responses observed in co-axial bioassays cannot be attributed to hypoxia.
authors.affiliation: Department of Pharmacology, King's College London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Spina
authors.forename: L B
authors.initials: LB
authors.lastname: Fernandes
authors.forename: J M
authors.initials: JM
authors.lastname: Preuss
authors.forename: D W
authors.initials: DW
authors.lastname: Hay
authors.forename: R M
authors.initials: RM
authors.lastname: Muccitelli
authors.forename: C P
authors.initials: CP
authors.lastname: Page
authors.forename: R G
authors.initials: RG
authors.lastname: Goldie
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology; D001681:Biological Assay; D001685:Biological Factors / Q000032:analysis / Q000502:physiology; D019806:Cromakalim; D004848:Epithelium / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012143:Respiratory Physiological Phenomena
chemical_list: D001578:Benzopyrans; D001685:Biological Factors; D011758:Pyrroles; C067763:epithelium-derived inhibitory factor; D019806:Cromakalim; D007545:Isoproterenol; D005905:Glyburide