title: Reduced uterine perfusion pressure decreases functional capillary density in skeletal muscle.
abstract: The purpose of this study was to examine the functional and structural capillary density in the reduced uterine perfusion pressure (RUPP) model, which when performed during pregnancy is an established animal model of preeclampsia. We hypothesized that the RUPP model would be associated with capillary rarefaction and impaired capillary perfusion, which would be more pronounced in the pregnant state. Female Sprague-Dawley rats (n = 32) were randomized to nonpregnancy (Nonpregnant) or breeding (Pregnant) at 12 wk of age and again to RUPP or SHAM surgeries on gestational day (GD) 14 (or equivalent age in nonpregnant rats). On GD 20 (or equivalent), capillary structure and perfusion of the extensor digitorum longus were imaged using digital intravital video microscopy. Functional videos were analyzed by a blinded observer to measure capillary density, expressed as capillaries per millimeter intersecting three staggered reference lines (200 μm). Flow was scored as the percentage of capillaries having 1) continuous, 2) intermittent, or 3) stopped flow. Total capillary density was not different between groups. There was a main effect of RUPP surgery resulting in decreased continuous flow vessels (P < 0.01) and increased stopped flow (P < 0.01), which was driven by differences between pregnant animals (Continuous flow: pregnant SHAM 80.1 ± 7.8% vs. pregnant RUPP 67.8 ± 11.2%, P < 0.05) (Stopped flow: pregnant SHAM 8.7 ± 3.2% vs. pregnant RUPP 17.9 ± 5.7%, P < 0.01). Our results demonstrate that the RUPP surgery is associated with a decrease in functional capillary density in skeletal muscle that is more pronounced in the pregnant state, which may contribute to the vascular pathophysiology observed in preeclampsia.
authors.affiliation: Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada;
authors.forename: Graham M
authors.initials: GM
authors.lastname: Fraser
authors.affiliation: Department of Obstetrics & Gynecology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada;
authors.forename: Jude S
authors.initials: JS
authors.lastname: Morton
authors.affiliation: Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada; Program for Pregnancy and Postpartum Health, Physical Activity and Diabetes Laboratory, Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada; and.
authors.forename: Sydney M
authors.initials: SM
authors.lastname: Schmidt
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada;
authors.forename: Stephane
authors.initials: S
authors.lastname: Bourque
authors.affiliation: Department of Obstetrics & Gynecology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada;
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
authors.affiliation: Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada; Program for Pregnancy and Postpartum Health, Physical Activity and Diabetes Laboratory, Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada; and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Margie H
authors.initials: MH
authors.lastname: Davenport
authors.affiliation: Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada; Program for Pregnancy and Postpartum Health, Physical Activity and Diabetes Laboratory, Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada; and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada craig.steinback@ualberta.ca.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Steinback
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002196:Capillaries / Q000033:anatomy & histology / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb / Q000601:surgery; D018715:Microscopy, Video; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000098:blood supply*; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D014599:Uterus / Q000033:anatomy & histology / Q000098:blood supply* / Q000601:surgery
keywords: RUPP model; capillary function; preeclampsia; pregnancy