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

被引:6
作者
Stirrat, A. [1 ]
Nelli, S. [1 ]
Dowell, F. J. [2 ]
Martin, W. [1 ]
机构
[1] Univ Glasgow, Inst Biomed & Life Sci, Div Neurosci & Biomed Syst, Glasgow G12 8QQ, Lanark, Scotland
[2] Univ Glasgow, Sch Vet, Inst Comparat Med, Glasgow G12 8QQ, Lanark, Scotland
基金
英国惠康基金;
关键词
artery; ascorbate; EDHF; endothelium; endothelium-derived hyperpolarizing factor; flow; nitric oxide; vasodilatation;
D O I
10.1038/sj.bjp.0707499
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1162 / 1168
页数:7
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