Abstract
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.
Footnotes
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Send reprint requests to: Ki Whan Hong, M.D., Ph.D., Department of Pharmacology, College of Medicine, Pusan National University, 10 Ami-Dong, 1-Ga, Seo-Gu, Pusan 602-739, South Korea. E-mail: kwhong{at}pusan.ac.kr
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This study was supported by funds from Center for Bioactive Substances, Korea Ministry of Science and Technology.
- Abbreviations:
- AII
- angiotensin II
- VEGF
- vascular endothelial growth factor
- PBS
- phosphate-buffered saline
- AT1
- angiotensin II type 1 receptor
- Received August 10, 2000.
- Accepted November 29, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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