title: Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.
abstract: Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+/-3 versus 92+/-1 [NP] and 93+/-3% [sham], P<0.01; bradykinin: 40+/-2 versus 62+/-2 [NP] and 59+/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+/-7 versus 86+/-2%, P<0.05; bradykinin: 35+/-5 versus 55+/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+/-7 versus 63+/-7%, ns; bradykinin: 37+/-5 versus 35+/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.
authors: Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland. S.Walsh@ucc.ie
authors: Sarah K
authors: SK
authors: Walsh
authors: Fred A
authors: FA
authors: English
authors: Edward J
authors: EJ
authors: Johns
authors: Louise C
authors: LC
authors: Kenny
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion / Q000379:methods; D010920:Placenta / Q000098:blood supply; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011312:Pressure; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester