BACKGROUND AND PURPOSE Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1. EXPERIMENTAL APPROACH SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24 h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O 2•-) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR, ethidium fluorescence and elisa, respectively. KEY RESULTS I/R increased ET-1 plasma concentration, ET-1-mediated vasoconstriction and ET B mRNA expression, and down-regulated ET A mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ET B receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ET B receptor agonist sarafotoxin-6 induced a contraction that was inhibited by the ET B receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET-1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET-1 vasoconstriction by BQ788. Endothelium removal, N ω-nitro-L-arginine methyl ester and superoxide dismutase abolished the differences in ET-1 vasoconstriction between sham and I/R rats. We also found that I/R down-regulates endothelial NOS mRNA expression and concomitantly enhanced O 2•- production by increasing NADPH oxidase 1 (NOX-1) and p 47phox mRNA. CONCLUSIONS AND IMPLICATIONS Mesenteric I/R potentiated the ET-1-mediated vasoconstriction by a mechanism that involves up-regulation of muscular ET B receptors and decrease in NO bioavailability. © 2011 The British Pharmacological Society.
- ET receptor A
- ET receptor B
- mesenteric resistance arteries