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Differential effect of innate immune system activation during pregnancy on cerebral vascular structure and function
Author(s) -
Cipolla Marilyn J.,
Houston Emily P.,
Kraig Richard P.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.836.14
Low‐dose endotoxin causes preeclamptic‐like symptoms in pregnant animals but not nonpregnant, demonstrating the immune‐sensitizing effects of pregnancy. We investigated the effect of low‐dose endotoxin on the function and structure of posterior cerebral arteries (PCA). Nonpregnant (NP) or late‐pregnant (LP) Wistar rats (n=8/group) were treated i.v. for 1 hour with 1.5μg/mL lipopolysaccharide (LPS; LP‐LPS) or vehicle (LP‐CTL) on d14 of pregnancy or 5 days prior to use for nonpregnant (NP‐CTL, NP‐LPS). On d19 of pregnancy, PCA were isolated and studied pressurized. LPS treatment of NP animals had little effect on lumen diameter, wall thickness, myogenic tone or nitric oxide (NO) responsiveness. However, LPS treatment of pregnant animals decreased myogenic tone (at 75mmHg: 44±10% for LP‐CTL vs. 14±5% for LP‐LPS;p<0.05) and increased active lumen diameter (at 75mmHg: 138±10 μm for LP‐CTL vs. 175±13 μm for LP‐LPS;p<0.05). In addition, LP‐LPS animals were more sensitive to the NO donor NONOate (EC50=30±9nM vs. 12±2nM; p=0.06). LPS did not affect blood pressure in any group, but nonsignificantly decreased pup weights in LP‐LPS animals. These results demonstrate that pregnancy is exquisitely sensitive to innate immune system activation that may contribute to neurological complications during immune challenging conditions such as preeclampsia. Supported by NS045940 (to MJC) and NS19108 (to RPK).