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. 2020 Oct:22:151-155.
doi: 10.1016/j.preghy.2020.09.002. Epub 2020 Sep 11.

17-Hydroxyprogesterone caproate improves hypertension and renal endothelin-1 in response to sFlt-1 induced hypertension in pregnant rats

Lorena M Amaral  1 , Jesse N Cottrell  2 , Kyleigh M Comley  3 , Mark W Cunningham Jr  3 , Alexis Witcher  3 , Venkata Ramana Vaka  3 , Tarek Ibrahim  3 , Babbette LaMarca  3
Affiliations

17-Hydroxyprogesterone caproate improves hypertension and renal endothelin-1 in response to sFlt-1 induced hypertension in pregnant rats

Lorena M Amaral et al. Pregnancy Hypertens. 2020 Oct.

Abstract

Preeclampsia (PE) is characterized by new onset hypertension in association with elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and preproendothelin-1 (PPET-1) levels. Currently there is no effective treatment for PE except for early delivery of the fetal placental unit, making PE a leading cause for premature births worldwide. Administration of 17-hydroxyprogesterone caproate (17-OHPC) is used for prevention of recurrent preterm birth. This study was designed to test the hypothesis that 17-OHPC improves hypertension and ET-1 in response to elevated sFlt-1 in pregnant rats. sFlt-1 was infused into normal pregnant (NP) Sprague-Dawley rats (3.7 μg·kg-1·day-1 for 6 days, gestation days 13-19) in the presence or absence of 17-OHPC (3.32 mg/kg) administered via intraperitoneal injection on gestational days 15 and 18. Mean arterial blood pressure (MAP), pup and placenta weights, renal cortex PPET-1 mRNA levels and nitrate-nitrite levels were measured on GD 19. Infusion of sFlt-1 into NP rats elevated mean arterial pressure (MAP) compared with control NP rats: 115 ± 1 (n = 13) vs. 99 ± 2 mmHg (n = 12, p < 0.05). 17-OHPC attenuated this hypertension reducing MAP to 102 ± 3 mmHg in sFlt-1 treated pregnant rats (n = 8). Neither pup nor placental weight was affected by sFlt-1 or 17-OHPC. Importantly, renal cortex PPET-1 mRNA levels were elevated 3 fold in NP + sFlt-1 rats compare to NP rats, which decreased with 17-OHPC administration. Plasma nitrate-nitrite levels were 44 ± 9 µM in NP rats (n = 9), 20 ± 3 µM in NP + sFlt-1 (n = 7), which increased to 42 ± 11 µM NP + sFlt-1 + 17OHPC (n = 6). Administration of 17-OHPC improves clinical characteristics of preeclampsia in response to elevated sFlt-1 during pregnancy.

Keywords: 17-OHPC; Preeclampsia; Preproendothelin-1; sFlt-1.

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Conflict of interest statement

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
17-OHPC reduces mean arterial blood pressure (MAP) in response to sFlt-1 induced hypertension in pregnant rats (n = 11–17/group). Data are shown as means ± S.E.M. *p < 0.05 vs. NP, #p < 0.05 vs. NP + sFlt-1. One-way ANOVA and Bonferroni as post hoc analysis were performed to generate p values.
Fig. 2.
Fig. 2.
17-OHPC did not change either pup (panel A) or placenta weights (panel B) in response to sFlt-1 induced hypertension in pregnant rats (n = 11–17/group). Data are shown as means ± S.E.M. One-way ANOVA and Bonferroni as post hoc analysis were performed to generate p values.
Fig. 3.
Fig. 3.
17-OHPC improves renal cortex PPET-1 (n = 5–7/group). Data are shown as means ± S.E.M. *p < 0.05 vs. NP, #p < 0.05 vs. NP + sFlt-1. One-way ANOVA and Bonferroni as post hoc analysis were performed to generate p values.
Fig. 4.
Fig. 4.
17-OHPC increases circulating nitrate-nitrite levels (n = −6–9/group) in response to sFlt-1 during pregnancy. Data are shown as means ± S.E.M. One-way ANOVA and Bonferroni as post hoc analysis were performed to generate p values.
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References

    1. Creasy RK, Resnik R, Greene MF, Iams JD, Lockwood CJ, Creasy and resnik’s maternal-fetal medicine: principles and practice.1 online resource.
    1. Duley L, Maternal mortality associated with hypertensive disorders of pregnancy in africa, asia, latin america and the caribbean, Br. J. Obstet. Gynaecol 99 (1992) 547–553. - PubMed
    1. Noris M, Perico N, Remuzzi G, Mechanisms of disease: pre-eclampsia, Nat. Clin. Practice Nephrol 1 (2005) 98–114, quiz 120. - PubMed
    1. American College of O, Gynecologists, Task Force on Hypertension in P. Hypertension in pregnancy. Report of the American college of obstetricians and gynecologists’ task force on hypertension in pregnancy. Obstet. Gynecol 122 (2013) 1122–1131. - PubMed
    1. Schlembach D, Pre-eclampsia–still a disease of theories, Fukushima J. Med. Sci 49 (2003) 69–115. - PubMed

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