Research Paper
Subject Category: Cardiovascular and pulmonary pharmacology
British Journal of Pharmacology (2008) 153, 1162–1168; doi:10.1038/sj.bjp.0707499; published online 8 October 2007
Flow-induced enhancement of vasoconstriction and blockade of endothelium-derived hyperpolarizing factor (EDHF) by ascorbate in the rat mesentery BJPOpen
A Stirrat1, S Nelli1, F J Dowell2 and W Martin1
- 1Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK
- 2Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow, Scotland, UK
Correspondence: Professor W Martin, Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK. E-mail: W.Martin@bio.gla.ac.uk
Received 4 July 2007; Revised 30 August 2007; Accepted 5 September 2007; Published online 8 October 2007.
Abstract
Background and purpose:
We previously reported that ascorbate inhibits flow- and agonist-induced, EDHF-mediated vasodilatation in the bovine ciliary circulation. This study examined whether ascorbate had similar actions in the rat mesenteric vasculature.
Experimental approach:
The effects of ascorbate were examined both in rat second order mesenteric arterial rings suspended in a static wire myograph and the rat mesentery perfused at different rates of flow.
Key results:
Ascorbate (50 
M) had no effect on U46619-induced tone or acetylcholine-induced, EDHF-mediated vasodilatation in either rings of mesenteric artery or the perfused mesentery at rates of flow below 10 ml min-1. At higher rates of flow, ascorbate produced two distinct effects in the rat mesentery: a rapid and maintained enhancement of vasoconstrictor tone and a slow (max at 3 h) inhibition of acetylcholine-induced, EDHF-mediated vasodilatation. The enhancement of vasoconstrictor tone appeared to be due to inhibition of flow-induced EDHF-like activity, since it was endothelium-dependent, but could be elicited during blockade of nitric oxide synthase and cyclooxygenase. Despite this, the classical inhibitors of EDHF, apamin and charybdotoxin, failed to affect the ascorbate-induced enhancement of tone, although they inhibited acetylcholine-induced vasodilatation.
Conclusions and implications:
Ascorbate inhibits both flow- and agonist-induced EDHF in the rat mesentery. The strikingly different timecourses of these two effects, together with their differential sensitivity to apamin and charybdotoxin, suggest that the flow- and agonist-induced EDHFs in the rat mesenteric vasculature may either be different entities or operate by different mechanisms.
Keywords:
artery, ascorbate, EDHF, endothelium, endothelium-derived hyperpolarizing factor, flow, nitric oxide, vasodilatation
Abbreviations:
CHAPS, 3-[(cholamidopropyl)dimethyl-ammonio]1-propanesulphonate; EDHF, endothelium-derived hyperpolarizing factor; L-NAME, NG-nitro-L-arginine methyl ester
