The aim of this study was to assess the in vivo rat pial microvascular responses induced by Apigenin (natural flavonoid) during hypoperfusion-reperfusion injury (H/R). Pial microcirculation was observed by fluorescence microscopy, hypoperfusion was induced by bilateral common carotid artery occlusion (BCCAO) for 30 min followed by 60 min of reperfusion. Arteriolar diameter, permeability increase, leukocyte adhesion, perfused capillary length (PCL) and capillary red blood cell velocity (VRBC) were evaluated. Pial arterioles were classified by Strahler's ordering scheme. Apigenin (10 - 20 mg/kg b.w.) or L-N5-(1-Iminoethyl) Ornithine Hydrochloride (L-NIO: 15 mg/Kg b.w.) prior to Apigenin was intravenously administered before BCCAO and at beginning of reperfusion.

In ischemic rats, BCCAO caused decrease in order 2 arteriole diameter, that was reduced by 12.5 ± 1.5 % of baseline at the end of reperfusion (RE). Microvascular permeability and leukocyte adhesion were marked. PCL and VRBC decreased at RE.

At the end of BCCAO, Apigenin reverted order 2 arteriolar diameter decrease, causing vasodilation at RE. Microvascular leakage and leukocyte adhesion were prevented at RE. L-NIO prior to Apigenin abolished the Apigenin-induced effects. Western blotting showed that at RE eNOS protein concentration significantly increased in rats treated with Apigenin.

Apigenin dose-dependently preserved pial microcirculation during H/R. Moreover, Apigenin's effects may be mediated by eNOS activation.