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Ascorbate blocks endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine ciliary
Alister J McNeish1, William S Wilson, William Martin
1Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ.
Insights
Vitamin C (ascorbate) blocks endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation in bovine eyes and rat mesenteric arteries. This effect, observed at physiological concentrations, suggests a significant role for ascorbate in regulating vascular tone.
Area of Science:
- Vascular Biology
- Pharmacology
- Biochemistry
Background:
- Endothelium-derived hyperpolarizing factor (EDHF) plays a crucial role in regulating vascular tone.
- Ascorbate (Vitamin C) is a potent antioxidant with potential effects on vascular function.
- The impact of ascorbate on EDHF-mediated responses requires further elucidation.
Purpose of the Study:
- To investigate the effects of ascorbate on EDHF-mediated vasodilatation.
- To determine the influence of ascorbate on vascular responses in the bovine ciliary vascular bed and rat mesenteric arterial bed.
Main Methods:
- Isolated perfused bovine eye and rat mesenteric arterial bed models were used.
- Vasodilator responses to acetylcholine and bradykinin were measured.
- The effects of ascorbate, N-acetyl-L-cysteine, dithiothreitol, and dehydroascorbate on these responses were assessed.
Main Results:
- Ascorbate significantly blocked EDHF-mediated vasodilatation in both bovine and rat models in a time- and concentration-dependent manner.
- A muscarinic vasoconstrictor response to acetylcholine was unmasked by ascorbate in the bovine eye.
- The blocking effect of ascorbate was mimicked by other reducing agents but not by a redox-inactive analogue, suggesting a role for its reducing properties.
Conclusions:
- Physiological concentrations of ascorbate can inhibit EDHF-mediated vasodilator responses.
- This blockade occurs in both ocular and mesenteric vascular beds.
- The precise mechanism and physiological implications of ascorbate-induced blockade of EDHF signaling warrant further investigation.
Abstract:
1. The effects of ascorbate were assessed on vasodilatation mediated by endothelium-derived hyperpolarizing factor (EDHF) in the ciliary vascular bed of the bovine isolated perfused eye and in the rat isolated perfused mesenteric arterial bed. 2. In the bovine eye, EDHF-mediated vasodilator responses induced by acetylcholine or bradykinin were powerfully blocked when ascorbate (50 microM) was included in the perfusion medium for at least 120 min; with acetylcholine a normally-masked muscarinic vasoconstrictor response was also uncovered. 3. The blockade of EDHF-mediated vasodilatation by ascorbate was time-dependent (maximum blockade at 120 min) and concentration-dependent (10 - 150 microM). 4. Ascorbate (50 microM) also blocked acetylcholine-induced, EDHF-mediated vasodilator responses in the rat mesenteric arterial bed in a time-dependent manner (maximum blockade at 180 min). 5. The ability of ascorbate to block EDHF-mediated vasodilatation is likely to result from its reducing properties, since this action was mimicked in the bovine eye by two other reducing agents, namely, N-acetyl-L-cysteine (1 mM) and dithiothreitol (100 microM), but not by the redox-inactive analogue, dehydroascorbate (50 microM). 6. In conclusion, concentrations of ascorbate present in normal plasma block EDHF-mediated vasodilator responses in the bovine eye and rat mesentery. The mechanism and physiological consequences of this blockade remain to be determined.