Vol. 296, Issue 3, 1085-1090, March 2001

Antiangiogenic Effect of KR31372 in Rat Sponge Implant Model

Chi Dae Kim, Hyung Hwan Kim, Yong Ki Kim , Yong Keun Kwak, Sun-Ok Kim, Sung-Eun Yoo and Ki Whan Hong

Department of Pharmacology (C.D.K., H.H.K., K.W.H.) and Nuclear Medicine (Y.K.K), College of Medicine, Pusan National University, Pusan, Korea; College of Medicine, Chonbuk National University, Chonbuk, Korea (Y.K.K); Central Research Institute of Dongbu Hannong Chemical Co., Daejon, Korea (S.-O.K); and Research Institute of Chemical Technology, Daejon, Korea (S.-E.Y)

A rat sponge implant model was used to examine the antiangiogenic effect of KR31372. Topical administration of angiotensin II (AII, 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 AII-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 AII, 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 AII-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.