Antiangiogenic effect of KR31372 in rat sponge implant model

A rat sponge implant model was used to examine the antiangiogenic effect of KR31372. Topical administration of angiotensin II (All, 100 ng, daily) into the sponges enhanced the basal sponge-induced neovascularization, leading to higher clearance of ^99mTc, increased retention of dye in the vessels, and increased numbers of blood vessels. These All-induced changes were significantly suppressed by oral administration of KR31372 (1 mg/kg for 7 days). Angiogenic effect of recombinant human VEGF₁₆₅ (200 ng) was modestly higher than that of All, which was also significantly inhibited by KR31372. KR31372-mediated suppression of ^99mTc clearance was reversed by glibenclamide. Levcromakalim showed a modestly suppressive effect on the All-induced angiogenesis. In conclusion, KR31372 exerted a strong inhibitory effect on the sponge-induced neovascularization, in part, through mediation of glibenclamide-sensitive K⁺ channel activation. It is suggested that it may have therapeutic potential in the treatment of angiogenic disorders.