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Updated: Aug 23, 2026
Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
Published on: July 16, 2013
Requirement for flow in the blockade of endothelium-derived hyperpolarizing factor (EDHF) by ascorbate in the bovine
Silvia Nelli1, Fiona J Dowell, William S Wilson
1Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, Scotland.
Insights
Ascorbate inhibits endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation in bovine ciliary arteries under flow conditions, but not in static myograph preparations. This flow-dependent inhibition highlights a novel interaction between physiological flow and ascorbate
Area of Science:
- Vascular Physiology
- Pharmacology
Background:
- Endothelium-derived hyperpolarizing factor (EDHF) mediates vasodilation.
- Ascorbate previously showed variable effects on EDHF-mediated vasodilation in different vascular preparations.
- The role of physiological conditions like flow in ascorbate's action is unclear.
Purpose of the Study:
- To compare ascorbate's effect on EDHF-mediated vasodilation in perfused versus static bovine ciliary arteries.
- To investigate the influence of flow rate on ascorbate's inhibitory action.
Main Methods:
- Utilized perfused bovine long posterior ciliary arteries and myograph preparations.
- Administered bradykinin and acetylcholine to induce vasodilation.
- Employed blocking agents (apamin/charybdotoxin, L-NAME) to identify EDHF and nitric oxide contributions.
- Tested varying concentrations of ascorbate under different flow conditions and in static myographs.
Main Results:
- Ascorbate inhibited EDHF-mediated vasodilation in perfused segments but not in myograph rings.
- Inhibition was time-dependent and occurred at higher flow rates (≥2.5 ml/min).
- Ascorbate's inhibitory effect was directly related to flow, independent of pressure changes.
Conclusions:
- Ascorbate inhibits EDHF-mediated vasodilation in a flow-dependent manner in the bovine ciliary artery.
- Static myograph preparations do not replicate the flow-dependent inhibitory effects of ascorbate.
- The mechanism underlying flow-induced susceptibility of EDHF to ascorbate inhibition requires further investigation.
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.
