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 (AII, 100 ng, daily) into the sponges enhanced the basal sponge-induced neovascularization, leading to higher clearance of (99m)Tc, 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 VEGF(165) (200 ng) was modestly higher than that of AII, which was also significantly inhibited by KR31372. KR31372-mediated suppression of (99m)Tc 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.
Kim
C D
CD
Department of Pharmacology, College of Medicine, Pusan National University, Pusan, Korea.
Kim
H H
HH
Kim
Y K
YK
Kwak
Y K
YK
Kim
S
S
Yoo
S
S
Hong
K W
KW
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000804:Angiotensin II; D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D016228:Endothelial Growth Factors / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D019736:Prostheses and Implants; D051381:Rats; D015503:Surgical Sponges; D013667:Technetium / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D001578:Benzopyrans; D016228:Endothelial Growth Factors; D007004:Hypoglycemic Agents; C419651:KR 31372; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000804:Angiotensin II; D013667:Technetium; D005905:Glyburide