title: Differential effects of low-dose endotoxin on the cerebral circulation during pregnancy.
abstract: It is well-known that the pregnant state is associated with increased sensitivity to endotoxin in renal and uterine circulations; however, the effects on the cerebral circulation are not known. Intravenous infusion of low-dose lipopolysaccharide ([LPS]; 1.5 μg/kg) to pregnant Wistar rats on day 15 of pregnancy caused significantly decreased myogenic tone of posterior cerebral arteries on day 20, which was not seen in similarly treated nonpregnant rats. Pregnancy alone was associated with a 2-to 4-fold increase in inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) messenger RNA (mRNA) in cerebral arteries compared to nonpregnant, suggesting that the cerebral circulation is in a state of inflammation during pregnancy. After LPS treatment, cerebral arteries from pregnant animals had increased iNOS and TNF-α compared to LPS-treated nonpregnant animals, but decreased interleukin 10 (IL-10) and IFN-γ. These results demonstrate that pregnancy enhances sensitivity to the effects of LPS in the cerebral circulation, which may be due to an enhanced inflammatory state during pregnancy.
authors.affiliation: Department of Neurology, University of Vermont College of Medicine, Burlington, VT 05405, USA. Marilyn.Cipolla@uvm.edu
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Cipolla
authors.forename: Emily M
authors.initials: EM
authors.lastname: Houston
authors.forename: Richard P
authors.initials: RP
authors.lastname: Kraig
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bonney
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002536:Cerebral Arteries / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007262:Infusions, Intravenous; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004731:Endotoxins; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D016753:Interleukin-10; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat