title: Nitric oxide induces vascular endothelial growth factor expression in the rat placenta in vivo and in vitro.
abstract: We investigated the role of nitric oxide (NO) in vascular endothelial growth factor (VEGF) expression in the rat placenta. A nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine-methyl ester (L-NAME), was constantly infused into pregnant rats 6-24 h before sacrifice on gestational day (GD) 15.5. NO production declined to about 15% of the control level as monitored by NO trapping and electron paramagnetic resonance spectroscopy. VEGF mRNA expression was temporally decreased by L-NAME, but recovered to normal levels after 24 h of treatment, whereas hypoxia inducible factor (HIF)-1α and induced NOS (iNOS) expression increased. VEGF expression decreased significantly in placental explants after 6 h of co-treatment with L-NAME and lipopolysaccharide, an iNOS inducer. Our data indicate that NO induce VEGF expression in vivo and in vitro in the rat placenta, suggesting that peaked NO production was maintained by a reciprocal relationship between NO and VEGF via HIF-1α.
authors: Graduate School of Veterinary Medicine, Azabu University, Fuchinobe, Chuo-ku, Sagamihara, Japan.
authors: Hideaki
authors: H
authors: Abe
authors: Wataru
authors: W
authors: Ishikawa
authors: Takahiro
authors: T
authors: Kushima
authors: Tomoka
authors: T
authors: Nishimura
authors: Chiemi
authors: C
authors: Mori
authors: Atsushi
authors: A
authors: Onuki
authors: Takehito
authors: T
authors: Suzuki
authors: Yasuo
authors: Y
authors: Ishii
authors: Norio
authors: N
authors: Kansaku
authors: Yoko
authors: Y
authors: Miyazaki
authors: Kazuaki
authors: K
authors: Tanaka
authors: Hidetoshi
authors: H
authors: Morita
authors: Tatsuya
authors: T
authors: Takizawa
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D019331:NG-Nitroarginine Methyl Ester