Pregnancy augments uteroplacental vascular endothelial growth factor gene expression and vasodilator effects.
This study examined a potential role for vascular endothelial growth factor (VEGF) in uterine artery remodeling and vasodilation during pregnancy. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect VEGF mRNA in uterine tissues from nonpregnant (NP), midpregnant (MP, 15-16 days), and late-pregnant (LP, 19-21 days) rats and in placentas from MP and LP rats. VEGF mRNA levels in uteri and placentas were determined by Northern blotting, and the vasorelaxant activity of recombinant human VEGF (rh-VEGF) was tested and compared in isolated uterine arteries from LP and NP animals. VEGF120 and VEGF164 were the major isoforms detected in uterine tissues; all members of the VEGF family (VEGF120, VEGF164, VEGF188, and VEGF205) were expressed in LP placentas. VEGF mRNA levels increased 60% in MP and 80% in LP above those in NP (P < 0.05) in uterine tissues; VEGF mRNA levels were also detectable in placentas and elevated approximately fivefold in LP vs. MP tissues (P < 0.01). Phenylephrine-preconstricted uterine arcuate arteries (NP and LP) dilated in response to rhVEGF, an effect that was completely abolished by endothelial denudation or pretreatment with genistein, a tyrosine kinase inhibitor. The magnitude of dilation to an intermediate concentration of rhVEGF (1 nM) was greater in LP than in NP vessels (55 +/- 8 vs. 24 +/- 11%; P < 0.05), and this effect was diminished comparably in both groups (approximately 60% by N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis. These results suggest that VEGF may play a role in the vascular remodeling and vasodilation that lead to decreased uterine vascular resistance and increased uterine blood flow during pregnancy.
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Department of Molecular Physiology and Biophysics, University of Vermont College of Medicine, Burlington 05405, USA.
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Braas
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Osol
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D000818:Animals; D001158:Arteries / Q000502:physiology; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014599:Uterus / Q000098:blood supply / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000502:physiology*
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide