Irradiation dose-response effects on angiogenesis and involvement of nitric oxide.
BACKGROUND
Recent results implicate nitric oxide (NO) in the irradiation-induced perturbation of angiogenic mechanisms. We have previously shown, using the chick embryo chorioallantoic membrane (CAM) and a dose of 10 Gy, that the NO pathway is involved in X-ray-induced anti-angiogenicity. In the current study, we investigated the implication of NO in the effects of various doses (2-15 Gy) of irradiation on angiogenesis.


METHODS
X-irradiation, NO synthase inhibitors, NO releasing agent and the in vivo CAM angiogenesis model (disc and ring method) were used. The CAM areas were irradiated on the 9th or the 14th day of embryo development and the vascular density was determined morphologically.


RESULTS
Doses up to 5 Gy resulted in dose-dependent reduction of vascular density, whereas the NO synthase inhibitors, added immediately post-irradiation, protected the 9-day CAM from the above anti-angiogenic effects of irradiation. NO donor, under certain circumstances potentiated the effects of X-rays when applied to the 9-day CAM using the ring method.


CONCLUSIONS
These results confirm the implication of NO in the anti-angiogenic mechanism of X-rays and describe the dose-response pattern of NO involvement in this action.
Hadjimichael
Christos
C
Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Medicine, University of Patras, GR 26504, Patras, Greece. hadjimichael.chr.@cytanet.com.cy
Kardamakis
Dimitrios
D
Papaioannou
Stamatis
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D014965:X-Rays
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester