Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Dec;70(6):1250-1255.
doi: 10.1161/HYPERTENSIONAHA.117.09969. Epub 2017 Oct 30.

Continued Investigation Into 17-OHPC: Results From the Preclinical RUPP Rat Model of Preeclampsia

Lorena M Amaral  1 , Jessica L Faulkner  1 , Jamil Elfarra  1 , Denise C Cornelius  1 , Mark W Cunningham  1 , Tarek Ibrahim  1 , Venkata Ramana Vaka  1 , Jessica McKenzie  1 , Babbette LaMarca  2
Affiliations

Continued Investigation Into 17-OHPC: Results From the Preclinical RUPP Rat Model of Preeclampsia

Lorena M Amaral et al. Hypertension. 2017 Dec.

Abstract

Preeclampsia is characterized by elevated TNF-α (tumor necrosis factor-α), antiangiogenic factors, such as sFlt-1 (soluble vascular endothelial growth factor receptor 1), increased uterine artery resistance index, and decreased of NO during pregnancy. Previously we showed that 17-hydroxyprogesterone caproate (17-OHPC) administered into reduced uterine perfusion pressure (RUPP) rats on day 18 of gestation improved hypertension without improving pup weight. We hypothesized that earlier administration of 17-OHPC on day 15 of gestation could improve pathophysiology of preeclampsia and fetal outcomes in response to placental ischemia. Carotid catheters were inserted on day 18, and mean arterial blood pressure and samples were collected on day 19. Mean arterial blood pressure in normal pregnant rats was 102±2, 105±2 in normal pregnant+day 15 of gestation (GD15) 17-OHPC, 127±2 in RUPP and 112±1 mm Hg in RUPP+GD15 17-OHPC, P<0.05. Pup weight and litter size were improved from 1.9±0.05, 10.1±1.4 in RUPP to 2.1±0.07 g and 13.2±0.6 in RUPP+GD15 17-OHPC, P<0.05. Uterine artery resistance index was 0.8±0.03 in RUPP, which was decreased to 0.6±0.04 in RUPP+GD15 17-OHPC, P<0.05. Plasma TNF-α levels were 164±34 in RUPP and blunted to 29±9 pg/mL in RUPP+GD15 17-OHPC, P<0.05. Plasma nitrate-nitrite levels were 10.8±2.3 in RUPP rats and significantly increased to 25.5±5.2 µmol/L in RUPP+GD15 17-OHPC, P<0.05. sFlt-1 levels were 386±141 in RUPP rats, which were reduced to 110.2±11 in RUPP+17-OHPC, P<0.05. These data indicate that GD15 17-OHPC improves pathophysiology in RUPP rats, possibly via improving sFlt-1 reduced NO during pregnancy.

Keywords: humans; inflammation; nitric oxide; preeclampsia; pregnancy.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Early administration of 17-OHPC improves blood pressure in RUPP rats. Data are shown as means ± S.E.M. (n=10–17/group). Two-way ANOVA and Bonferroni as post hoc analysis were performed to generate p values. *P <0.05, two-way ANOVA
Figure 2
Figure 2
Early administration of 17-OHPC decreases circulating factors in RUPP rats. (A) Bar graph showing the TNF-α in RUPP rats. (B) Bar graph showing the plasma NOx in RUPP rats. (C) Bar graph showing the sFlt-1 levels. Data are shown as means ± S.E.M. (n=6–7/group). Two-way ANOVA and Bonferroni as post hoc analysis were performed to generate p values. *P <0.05, two-way ANOVA
Figure 3
Figure 3
Early administration of 17-OHPC improves uterine artery resistance index in RUPP rats. (A) Bar graph showing the UARI in pregnant rats. (B) Representative Doppler ultrasound waveforms for each group. Data are shown as means ± S.E.M. (n=4–5/group). Two-way ANOVA and Bonferroni as post hoc analysis were performed to generate p values. *P <0.05 versus NP group, two-way ANOVA.
Figure 4
Figure 4
Early administration of 17-OHPC improves fetal weight and litter size in RUPP rats.(A) Bar graph showing the pup weight in pregnant rats. (B) Bar graph showing litter size in pregnant rats. Data are shown as means ± S.E.M. (n=7–15/group). Two-way ANOVA, Bonferroni as post hoc analysis and T test were performed to generate p values. *P <0.05, two-way ANOVA, # P<0.05, T test.
See this image and copyright information in PMC

References

    1. World health organization. [Acessed february 6, 2015];Maternal mortality fact sheet no. 348. 2012 Available from: http://www.Who.Int/mediacentre/factsheets/fs348/en/
    1. Noris M, Perico N, Remuzzi G. Mechanisms of disease: Pre-eclampsia. Nature clinical practice. Nephrology. 2005;1:98–114. quiz 120. - PubMed
    1. George EM, Granger JP. Recent insights into the pathophysiology of preeclampsia. Expert review of obstetrics & gynecology. 2010;5:557–566. - PMC - PubMed
    1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365:785–799. - PubMed
    1. Granger JP, Alexander BT, Llinas MT, Bennett WA, Khalil RA. Pathophysiology of preeclampsia: Linking placental ischemia/hypoxia with microvascular dysfunction. Microcirculation. 2002;9:147–160. - PubMed

Substances