Nitric oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester retards vascular sprouting in angiogenesis.
The present study was designed to evaluate the role of nitric oxide (NO) for angiogenesis. Angiogenesis was elicited upon mouse cornea by chemical cautery with silver nitrate. Angiogenic activity was evaluated by measuring the length of vascular sprout with or without administration of NO synthase (NOS) inhibitor, N((G))-nitro-L-arginine-methyl ester (L-NAME). In the pericorneal plexus, a circulatory loop situated in the same topological situation for all individuals was selected to observe vascular sprouting. At 72 h after cauterization, the length of the longest vascular sprout was measured using the perfused whole-mount cornea. The length of nontreated mice (83 +/- 83 microm) was significantly longer than that of L-NAME treated mice (33 +/- 24.6 microm). To address the possible contribution of production of vascular endothelial growth factor (VEGF) and NO, we measured mRNAs of VEGF and inducible NOS. The mRNA level of VEGF increased to 170% of the nontreated level at 12 h after cauterization and returned to the nontreated level by 24 h after cauterization. mRNA of inducible NOS remained elevated 24 h after cauterization. These results suggest that the response of preexisting vessels to angiogenic stimulus via NO is of importance in the process of angiogenesis, i.e., vascular sprouting is promoted by NO production. This might be attributable to enhancement of an increase in vascular permeability and /or vasodilation via NO.
Kon
K
K
Department of Medical Laboratory Technology, Ehime College of Health Science, Ehime, Japan. kon@ehime-chs.ac.jp
Fujii
S
S
Kosaka
H
H
Fujiwara
T
T
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019331:NG-Nitroarginine Methyl Ester