Flow-induced enhancement of vasoconstriction and blockade of endothelium-derived hyperpolarizing factor (EDHF) by ascorbate in the rat mesentery.
Br J Pharmacol
; 153(6): 1162-8, 2008 Mar.
Article
em En
| MEDLINE
| ID: mdl-17922023
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
Ascorbate (50 microM) 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Ascórbico
/
Vasodilatação
/
Fatores Biológicos
/
Antioxidantes
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Reino Unido