title: Requirement for flow in the blockade of endothelium-derived hyperpolarizing factor (EDHF) by ascorbate in the bovine ciliary artery.
abstract: We previously reported that ascorbate inhibits endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine perfused ciliary circulation and rat perfused mesentery, but not in rings of bovine or porcine coronary artery. In this study, we have compared the ability of ascorbate to inhibit EDHF-mediated vasodilatation in a single vessel, the bovine long posterior ciliary artery, when perfused and when mounted as rings in a myograph. Both in segments perfused at a flow rate of 2.5 ml min(-1) and in rings mounted in a myograph, bradykinin and acetylcholine each induced vasodilator responses that were mediated jointly by EDHF and nitric oxide, as revealed by their respective blocking agents, apamin/charybdotoxin, and L-NAME. Ascorbate (50 and 150 microm) induced a time (max at 2-3 h)-dependent inhibition of the EDHF-mediated component of vasodilatation to bradykinin or acetylcholine in perfused segments, but not in rings. Ascorbate (50 microm) failed to inhibit bradykinin-induced vasodilatation at a flow rate of 1.25 ml min(-1) or below, but produced graded blockade at the higher flow rates of 2.5 and 5 ml min(-1). Furthermore, using a pressure myograph where pressure and flow were independently controlled, it was confirmed that the inhibitory action of ascorbate (150 microm) was directly related to flow per se and not any associated changes in pressure. Thus, we have shown in the bovine ciliary artery that ascorbate inhibits EDHF-mediated vasodilatation under conditions of flow but not in a static myograph. The mechanism by which flow renders EDHF susceptible to inhibition by ascorbate remains to be determined.
authors.affiliation: Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, Scotland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nelli
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Dowell
authors.forename: William S
authors.initials: WS
authors.lastname: Wilson
authors.forename: Alison
authors.initials: A
authors.lastname: Stirrat
authors.forename: William
authors.initials: W
authors.lastname: Martin
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001685:Biological Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D002417:Cattle; D019842:Ciliary Arteries / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009213:Myography; D012039:Regional Blood Flow; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D001205:Ascorbic Acid