Pregnancy-induced alterations of vascular function in mouse mesenteric and uterine arteries.
Normal pregnancy involves dramatic changes to maternal vascular function, while abnormal vascular adaptations may contribute to pregnancy-associated diseases such as preeclampsia. Many genetic mouse models have recently emerged to study vascular pathologies of pregnancy. However, vascular adaptations to pregnancy in normal mice are not fully understood. Thus, we studied changes in vascular reactivity during normal mouse pregnancy. We hypothesized that pregnant mice will have enhanced endothelial-dependent vasodilation compared with nonpregnant mice, via an enhancement of the nitric oxide synthase (NOS) prostaglandin H synthase (PGHS), and other endothelial-derived hyperpolarizing pathways. Late pregnant (Day 17-18) C57BL/6J mice (n = 10) were compared with nonpregnant mice (n = 7). Uterine and mesenteric arteries were mounted on a wire myograph system and assessed for endothelium-dependent (methacholine) and -independent (sodium nitroprusside; SNP) relaxation responses. Endothelial-dependent relaxation was enhanced in pregnant uterine and mesenteric arteries, which was blunted after the addition of inhibitors of the PGHS or NOS pathways. In nonpregnant mice, these pathways had no effect in modulating relaxation in uterine arteries, whereas vasodilation in mesenteric arteries was reduced only by NOS inhibition. Both uterine and mesenteric vessels had nonnitric oxide- and nonprostaglandin-mediated relaxation, but this relaxation was not enhanced during pregnancy. Endothelial-independent relaxation was also enhanced in pregnant uterine but not mesenteric arteries. Our data indicate that uterine and mesenteric arteries from pregnant mice have enhanced vasodilation. Understanding vascular adaptations to normal mouse pregnancy is crucial for interpreting changes that may occur in genetic mouse models.
Cooke
Christy-Lynn M
CL
Perinatal Research Centre, Department of Obstetrics/Gynecology, University of Alberta, Edmonton, Alberta, Canada T6G 252.
Davidge
Sandra T
ST
D000818:Animals; D051545:Cyclooxygenase 1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008565:Membrane Proteins; D008638:Mesenteric Arteries / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009213:Myography; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014599:Uterus / Q000098:blood supply*; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D009599:Nitroprusside; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D019331:NG-Nitroarginine Methyl Ester