Flow-induced enhancement of vasoconstriction and blockade of endothelium-derived hyperpolarizing factor (EDHF) by ascorbate in the rat mesentery

Stirrat, A., Nelli, S., Dowell, F.J. and Martin, W. (2008) Flow-induced enhancement of vasoconstriction and blockade of endothelium-derived hyperpolarizing factor (EDHF) by ascorbate in the rat mesentery. British Journal of Pharmacology, 153(6), pp. 1162-1168. (doi: 10.1038/sj.bjp.0707499)

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 mu 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

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Martin, Professor William
• Authors: Stirrat, A., Nelli, S., Dowell, F.J., and Martin, W.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: British Journal of Pharmacology
• ISSN: 0007-1188
• Published Online: 29 January 2009