title: Dominant role of an endothelium-derived hyperpolarizing factor (EDHF)-like vasodilator in the ciliary vascular bed of the bovine isolated perfused eye.
abstract: 1. The roles of the endothelium-derived nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating vasodilator responses to acetylcholine and bradykinin were assessed in the ciliary vascular bed of the bovine isolated perfused eye preparation. 2. Vasodilatation to acetylcholine or bradykinin was unaffected by the nitric oxide synthase inhibitor, L-NAME (100 microM), or the cyclo-oxygenase inhibitor, flurbiprofen (30 microM), but was virtually abolished following treatment with a high concentration of KCl (30 mM), or by damaging the endothelium with the detergent, CHAPS (0.3%, 2 min). 3. Acetylcholine-induced vasodilatation was unaffected by glibenclamide (10 microM), an inhibitor of ATP-sensitive K(+) channels (K(+)(ATP)), but was significantly attenuated by TEA (10 mM), a non-selective inhibitor of K(+) channels. 4. The small conductance calcium-sensitive K(+) channel (SK(+)(Ca)) inhibitor, apamin (100 nM), and the large conductance calcium-sensitive K(+) channel (BK(+)(Ca)) inhibitor, iberiotoxin (50 nM), had no significant effect on acetylcholine-induced vasodilatation. In contrast, the intermediate (IK(+)(Ca))/large conductance calcium-sensitive K(+) channel inhibitor, charybdotoxin (50 nM), powerfully blocked these vasodilator responses, and uncovered a vasoconstrictor response. 5. The combination of apamin (100 nM) with a sub-threshold concentration of charybdotoxin (10 nM) significantly attenuated acetylcholine-induced vasodilatation, but the combination of apamin (100 nM) with iberiotoxin (50 nM) had no effect. 6. In conclusion, blockade by a high concentration of KCl, by charybdotoxin, or by the combination of apamin with a sub-threshold concentration of charybdotoxin, strongly suggests that vasodilatation in the bovine isolated perfused eye is mediated by an EDHF.
authors.affiliation: Division of Neuroscience & Biomedical systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, Scotland.
authors.forename: A J
authors.initials: AJ
authors.lastname: McNeish
authors.forename: W S
authors.initials: WS
authors.lastname: Wilson
authors.forename: W
authors.initials: W
authors.lastname: Martin
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D018999:Charybdotoxin / Q000494:pharmacology; D002924:Ciliary Body / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005123:Eye / Q000098:blood supply*; D005480:Flurbiprofen / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011312:Pressure; D011810:Quinoxalines / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D001685:Biological Factors; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001464:Barium; D010042:Ouabain; D005480:Flurbiprofen; D019789:Tetraethylammonium; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D011188:Potassium; D001920:Bradykinin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester