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. 2008 Dec;52(6):1161-7.
doi: 10.1161/HYPERTENSIONAHA.108.120881. Epub 2008 Nov 3.

Hypertension in response to chronic reductions in uterine perfusion in pregnant rats: effect of tumor necrosis factor-alpha blockade

Babbette LaMarca  1 , Josh Speed, Lillian Fournier, Sara A Babcock, Hunter Berry, Kathy Cockrell, Joey P Granger
Affiliations

Hypertension in response to chronic reductions in uterine perfusion in pregnant rats: effect of tumor necrosis factor-alpha blockade

Babbette LaMarca et al. Hypertension. 2008 Dec.

Abstract

Reductions in uterine perfusion pressure (RUPP) in pregnant rats is associated with increased tumor necrosis factor-alpha (TNF-alpha). This study was designed to determine the role of endogenous TNF-alpha in mediating changes in arterial pressure and endothelin-1 (ET-1) in RUPP rats. To achieve this goal we examined the effect of RUPP in the presence and absence of a TNF-alpha-soluble receptor, etanerecept (0.4 mg/kg). Mean arterial pressure increased from 102+/-1 mm Hg in normal pregnant (NP) rats to 134+/-3 mm Hg (P<0.05) in RUPP rats. Serum TNF-alpha increased to 40+/-7.6 pg/mL in RUPP rats (n=24) versus 14.8+/-3.3 pg/mL (n=16; P<0.05) in NP rats. Administration of etanerecept decreased TNF-alpha in RUPP rats (n=20) to 17.2+/-3 pg/mL and mean arterial pressure to 118+/-2 mm Hg (P<0.05). Tissue ET-1 decreased in etanerecept-treated RUPP rats compared with control RUPP rats. The direct effect of TNF-alpha blockade on endothelial activation in response to placental ischemia was examined in human umbilical vein endothelial cells. ET-1 secreted from human umbilical vein endothelial cells treated with RUPP serum was 59.2+16 pg/mg and decreased when etanerecept was added to the medium with RUPP serum (7.60+/-0.77 pg/mg), as well as in response to serum from etanerecept-treated RUPP rats (7.30+/-0.55 pg/mg; P<0.001). ET-1 secreted from human umbilical vein endothelial cells was 15.6+/-2 pg/mg when treated with NP serum. These data support the hypothesis that endogenous TNF-alpha is an important stimulus for ET-1 in response to placental ischemia and is important in mediating endothelial cell activation and hypertension during pregnancy.

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Figures

Figure 1
Figure 1
MAP and serum concentration of TNF-α in control pregnant rats (n=16), RUPP rats (n=24), control pregnant rats treated with etanerecept (n=15), and RUPP rats treated with etanerecept (n=20) at day 19 of gestation. *P<0.05 vs control pregnant rats; all of the data are expressed as means±SEMs.
Figure 2
Figure 2
Renal TNF-α messenger RNA level in RUPP rats (n=15) vs NP rats (n=14). *P<0.05 vs control pregnant rats. All of the data are expressed as means±SEMs.
Figure 3
Figure 3
Placental levels of TNF-α mRNA are elevated in RUPP rats (n=15) vs NP rats (n=14). TNF-α protein is elevated in placental tissue lysates in RUPP (n=5) vs NP (n=3) rats. *P<0.05 vs control pregnant rats. All of the data are expressed as means±SEMs.
Figure 4
Figure 4
Pup weights and placental weights in control pregnant rats (n=16), RUPP rats (n=24), control pregnant rats treated with etanerecept (n=15), and RUPP rats treated with etanerecept (n=20) at day 19 of gestation.*P<0.05 vs control pregnant rats. All of the data are expressed as means±SEMs.
Figure 5
Figure 5
Preproendothelin levels in the cortex, medulla, and placenta of control pregnant rats (n=5, n=9, n=7, respectively), NP rats treated with etanerecept (n=6, n=4, n=5, respectively), RUPP rats (n=6, P<0.02; n=7, P<0.004; n=6, P<0.011, respectively), and RUPP rats treated with etanerecept (n=9, n=5, n=10, respectively) at day 19 of gestation. *P<0.05 vs control pregnant rats. All of the data are expressed as means±SEMs.
Figure 6
Figure 6
ET-1 secretion from HUVECS at baseline and in response to etanerecept (E), to sera collected from control pregnant rats (n=14), control NP rats treated with etanerecept (n=8), sera from control pregnant rats with exogenous etanerecept added to the experimental media (n=12), RUPP rats (n=10; P<0.001), sera from RUPP rats treated with etanerecept (n=14), and sera from RUPP rats with exogenous etanerecept added to the experimental media (n=8). *P<0.001. All of the data are expressed as means±SEMs.
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References

    1. Minagawa M, Narita J, Tada T, Maruyama S, Shimizu T, Bannai M, Oya H, Hatakeyama K, Abo T. Mechanisms underlying immunologic states during pregnancy: possible association of the sympathetic nervous system. Cell Immunol. 1999;196:1–13. - PubMed
    1. Fisher SJ, Martin JM. Defects in placentation and placental perfusion. In: Lindheimer M, Roberts JM, Cunningham FG, editors. Chesley’s Hypertensive Disorders in Pregnancy. II Ed. Stamford, CT: Appleton and Lange; 1998. pp. 377–394.
    1. Ashworth JR, Baker PN, Warrend AY. Plasma from preeclamptic women induces a functional change in myometrial resisitance arteries. J Soc Gynecol Invest. 1997;4:71.
    1. August P, Lindheimer MD. Pathophysiology of preeclampsia. Hypertension. 1995;142:2407–2426.
    1. Roberts JM, Lain KY. Recent Insights into the pathogenesis of preeclampsia. Placenta. 2002;23:359–372. - PubMed

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