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Differential effects of ascorbate on endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the
Alister J McNeish1, Silvia Nelli, William S Wilson
1Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Insights
Ascorbate selectively blocks endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation in bovine ciliary vessels but not coronary arteries. This suggests EDHF mechanisms differ between these vascular beds.
Area of Science:
- Vascular Physiology
- Pharmacology
- Ophthalmology
Background:
- Endothelium-derived hyperpolarizing factor (EDHF) mediates important vasodilatory functions.
- The precise mechanisms and location-specific actions of EDHF are not fully understood.
- Ascorbate is investigated for its potential role in modulating vascular responses.
Purpose of the Study:
- To compare the inhibitory effects of ascorbate on EDHF-mediated vasodilation in bovine ciliary and coronary vascular beds.
- To determine if ascorbate acts as a universal blocker of EDHF.
- To elucidate potential differences in EDHF pathways between different vascular tissues.
Main Methods:
- Comparison of ascorbate's effects on acetylcholine- and bradykinin-induced vasodilation in perfused bovine ciliary artery and isolated coronary artery rings.
- Assessment of ascorbate's selectivity by testing its effects on nitric oxide- and K(ATP) channel-mediated vasodilation.
- Manipulation of fluid dynamics in the ciliary body to rule out ascorbate concentration as a factor in blockade.
Main Results:
- Low concentration ascorbate (50 micro M) selectively blocked EDHF-mediated vasodilation in the bovine ciliary circulation.
- Ascorbate at 50 micro M did not inhibit EDHF-mediated vasodilation in bovine coronary artery rings.
- Higher ascorbate concentration (3 mM) non-selectively inhibited vasodilation in coronary arteries, affecting both EDHF and nitric oxide pathways.
Conclusions:
- Ascorbate (50 micro M) is not a universal inhibitor of EDHF-mediated vasodilation.
- The differential effect of ascorbate suggests variations in EDHF mechanisms between ciliary and coronary circulations.
- Further research is needed to identify the factors contributing to these site-specific differences in EDHF activity.
Abstract:
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.
