Antiangiogenic effects of S-nitrosocaptopril crystals as a nitric oxide donor.
Angiogenesis is the formation of new capillaries from preexisting vessels by migration and proliferation of endothelial cells, which produce a cellular signaling messenger, nitric oxide (NO). The purpose of the present study was to examine the effects of exogenous NO donors on angiogenesis by using a novel crystalline NO donor, S-nitrosocaptopril. The characteristic X-ray diffraction pattern of S-nitrosocaptopril was demonstrated for the first time. On primary capillary endothelial cells pretreated with vascular endothelium growth factor (VEGF), S-nitrosocaptopril (1-500 microM), but not captopril, produced a dose-dependent inhibition of endothelial proliferation. On chick embryos of entire living eggs, gelatin sponges adsorbed with VEGF were implanted on the embryo chorioallantoic membrane to promote vascular growth activity within the sponges. Addition of S-nitrosocaptopril crystals (0.1 mg) to the gelatin sponges markedly reduced vascular density around the sponges, whereas captopril did not inhibit neovascularization. The vascular hemoglobin content surrounding each of the gelatin sponges was determined as a confirmatory test. S-nitrosocaptopril, but not captopril, significantly decreased the hemoglobin content of the embryo tissues immediately surrounding the gelatin sponges. In conclusion, S-nitrosocaptopril exerts an inhibitory effect on angiogenesis. This newly discovered function of S-nitrosocaptopril appears to be governed by distinct structural NO moiety.
Jia
L
L
La Jolla Pharmaceuticals, 11283 Carmel Creek Rd., San Diego, CA 92130, USA. lgia@access1.net
Wu
C C
CC
Guo
W
W
Young
X
X
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000502:physiology; D003460:Crystallization; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D014961:X-Ray Diffraction
D000806:Angiotensin-Converting Enzyme Inhibitors; D006454:Hemoglobins; D020030:Nitric Oxide Donors; C060039:S-nitrosocaptopril; D002216:Captopril