title: Vasodilation to vascular endothelial growth factor in the uterine artery of the pregnant rat is blunted by low dietary protein intake.
abstract: Pregnancy is associated with a substantial increase in uterine artery blood flow, which may in part result from dilation in response to vascular endothelial growth factor (VEGF). Uterine blood flow is reported to be reduced in globally diet-restricted pregnant rats. Both global and protein dietary restriction in pregnancy produce programmed effects in offspring. In this study we hypothesized that protein restriction in pregnancy impairs maternal uterine artery responses to VEGF. Vascular responses to VEGF were determined in isolated uterine arteries of pregnant (18 or 19 d of gestation) Wistar rats fed a diet containing either 18% or 9% casein throughout pregnancy. For comparison, responses to phenylephrine, potassium chloride, and acetylcholine were determined. In addition, the response of the mesenteric artery to VEGF was studied in the same animals. A significant reduction of the maximal relaxation to VEGF (p = 0.041) and in the overall response (p = 0.004) to VEGF was found in uterine arteries of the 9% compared with the 18% group, but responses to all other agonists were similar. The VEGF response was reduced by cyclooxygenase inhibition (indomethacin) in both groups. In the 18%, but not the 9%, group it was further reduced by nitric oxide synthase inhibition (Nomega-nitro-L-arginine methyl ester). VEGF was shown to dilate the mesenteric artery but this effect was not significantly altered by the low-protein diet. These results show an attenuated uterine artery vasodilator response to VEGF produced by a low-protein diet in pregnancy, partly because of a reduction of the nitric oxide component of VEGF-mediated relaxation.
authors.affiliation: Centre for Fetal Origins of Adult Disease, Princess Anne Hospital, University of Southampton, Southampton SO16 5YA, UK.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Itoh
authors.forename: Lee
authors.initials: L
authors.lastname: Brawley
authors.forename: Timothy
authors.initials: T
authors.lastname: Wheeler
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Anthony
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001835:Body Weight; D002317:Cardiovascular Agents / Q000494:pharmacology; D002364:Caseins / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011488:Protein Deficiency; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D002364:Caseins; D004044:Dietary Proteins; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; D011189:Potassium Chloride; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin