Nitric oxide regulates Angiopoietin1/Tie2 expression after stroke

We tested whether the nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio] diazen-1-ium-1,2-diolate (DETA-NONOate), increases expression of Angiopoietin (Ang1)/Tie2, which may play a role in regulating angiogenesis and vascular integrity after stroke in rats. Wistar rats were subjected to middle cerebral artery occlusion and treated with or without DETA-NONOate. Stroke rats treated with DETA-NONOate show significantly increased Ang1, Tie2 and Occludin expression in the ischemic border compared with control stroke animals (p < 0.05). Consistent with in vivo data, DETA-NONOate promotes capillary tube formation in cultured brain endothelial cells. Neutralizing Ang1 antibody attenuates DETA-NONOate-induced capillary tube formation. The data suggest that the Ang1/Tie2 axis promotes DETA-NONOate-induced angiogenesis and stabilizes of angiogenic vessels after stroke.