Endothelial dysfunction in rat mesenteric resistance artery after transient middle cerebral artery occlusion

Stroke triggers a local and systemic inflammatory response leading to the production of cytokines that can influence blood vessel reactivity. In this study, we aimed to assess whether cerebral ischemia/ reperfusion could affect vasoconstriction and vasodilatation on mesenteric resistance arteries ( MRA) from Wistar Kyoto rats. The right middle cerebral artery was occluded ( 90 min) and reperfused ( 24 h). Sham- operated animals were used as controls. Plasma levels of interleukin ( IL)- 6 and IL- 1 beta were measured at 24 h. Vasoconstrictor and vasodilator responses were recorded in a wire myograph. Protein expression was determined by Western blot and immunofluorescence, and superoxide anion ( O-2((.) over bar).) production was evaluated by ethidium fluorescence. In MRA, ischemia/ reperfusion increased plasma levels of IL- 6, O-2((.) over bar) production, protein expression of cyclooxygenase-2, and protein tyrosine nitrosylation, but it impaired acetylcholine (ACh) vasodilatation without modifying the vasodilatations to sodium nitroprusside or the contractions to phenylephrine and KCl. Superoxide dismutase ( SOD) and indomethacin reversed the impairment of ACh relaxation induced by ischemia/ reperfusion. However, N-omega- nitro-L-arginine methyl ester affected similarly ACh-induced vasodilatations in MRA of ischemic and sham-operated rats. Protein expression of endothelial and inducible nitric-oxide synthase, copper/zinc SOD, manganese SOD, and extracellular SOD was similar in both groups of rats. Our results show MRA endothelial dysfunction 24 h after brain ischemia/ reperfusion. Excessive production of O(2)((.) over bar)in MRA mediates endothelial dysfunction, and the increase in plasma cytokine levels after brain ischemia/ reperfusion might be involved in this effect.