Differential effects of ascorbate on endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine ciliary vascular bed and coronary artery.
1. The ability of ascorbate to inhibit endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation was compared in the bovine perfused ciliary vascular bed and isolated rings of coronary artery. 2. Acetylcholine-induced, EDHF-mediated vasodilatation of the ciliary circulation was blocked following inclusion of ascorbate (50 micro M, 120 min) in the perfusion fluid. The blockade was highly selective since ascorbate had no effect on the vasodilator actions of the K(ATP) channel opener, levcromakalim, nor on the tonic vasodepressor action of basally released nitric oxide. 3. The possibility that concentration of ascorbate by the ciliary body was a prerequisite for blockade to occur was ruled out, since EDHF was still blocked when the anterior and posterior chambers were continuously flushed with Krebs solution or when both the aqueous and vitreous humour were drained. 4. Ascorbate at 50 micro M failed to affect bradykinin- or acetylcholine-induced, EDHF-mediated vasodilatation in rings of bovine coronary artery. Raising the concentration to 3 mM did produce blockade of EDHF, but this was nonselective, since vasodilator responses to endothelium-derived nitric oxide were also inhibited. 5. Thus, ascorbate (50 micro M) is not a universal blocker of EDHF. Whether its ability to block in the bovine ciliary circulation, but not in the coronary artery, is due to differences in the nature of EDHF at the two sites, differences in vessel size (resistance arterioles versus conduit artery), the presence or absence of flow, or to some other factor remains to be determined.
McNeish
Alister J
AJ
Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Nelli
Silvia
S
Wilson
William S
WS
Dowell
Fiona J
FJ
Martin
William
W
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry / Q000187:drug effects; D001204:Ascorbate Oxidase / Q000494:pharmacology*; D001685:Biological Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D002417:Cattle; D019842:Ciliary Arteries / Q000187:drug effects; D002924:Ciliary Body / Q000098:blood supply / Q000187:drug effects*; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D024681:Potassium Channels, Calcium-Activated; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D024681:Potassium Channels, Calcium-Activated; C067410:endothelium-dependent hyperpolarization factor; D019806:Cromakalim; D001204:Ascorbate Oxidase; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D001920:Bradykinin