(Circulation. 1996;94:2566-2571.)
© 1996 American Heart Association, Inc.
Articles |
New Activity of Spironolactone
Inhibition of Angiogenesis In Vitro and In Vivo
the Department of Surgery, Children's Hospital and Harvard Medical School (N.K., F.B., B.A.-A., R.J.D.) and Department of Surgery, Boston Medical Center (N.K.), Boston, Mass.
Background The formation of new blood vessels (angiogenesis) is a critical component in a variety of pathological settings, including solid tumor growth, macular degeneration, and atherosclerosis.
Methods and Results We have found that orally administered spironolactone inhibited the area of angiogenesis induced by basic fibroblast growth factor (bFGF) in a rabbit corneal micropocket assay. Additionally, spironolactone inhibited bFGF- and vascular endothelial growth factor–stimulated capillary endothelial cell proliferation in vitro, inhibited bFGF-stimulated capillary endothelial cell chemotaxis in vitro, and caused avascular zones when placed on the chick chorioallantoic membrane. Experiments analyzing spironolactone metabolites revealed that the major human metabolites 6ß-hydroxy-7
-thiomethyl spironolactone and canrenoic acid retained antiangiogenic activity. The antiangiogenic activity appears to be unrelated to the antiandrogenic and antimineralocorticoid effects of spironolactone.
Conclusions These experiments hold promise for the potential use of spironolactone as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.
Key Words: angiogenesis • growth substances • endothelium • arteriosclerosis • diuretics
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