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

Lorena M. Amaral; Jesse N. Cottrell; Kyleigh M. Comley; Mark W. Cunningham; Alexis Witcher; Venkata Ramana Vaka; Tarek Ibrahim; Babbette LaMarca

doi:10.1016/j.preghy.2020.09.002

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

Lorena M. Amaral, Jesse N. Cottrell, Kyleigh M. Comley, Mark W. Cunningham, Alexis Witcher, Venkata Ramana Vaka, Tarek Ibrahim, Babbette LaMarca

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Pages (from-to)	151-155
Number of pages	5
Journal	Pregnancy Hypertension
Volume	22
DOIs	https://doi.org/10.1016/j.preghy.2020.09.002
State	Published - Oct 2020

Keywords

17-OHPC
Preeclampsia
Preproendothelin-1
sFlt-1

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10.1016/j.preghy.2020.09.002

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@article{e4a480f43a8f4d2d93379d6fbb27a585,

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

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",

author = "Amaral, {Lorena M.} and Cottrell, {Jesse N.} and Comley, {Kyleigh M.} and Cunningham, {Mark W.} and Alexis Witcher and Vaka, {Venkata Ramana} and Tarek Ibrahim and Babbette LaMarca",

note = "Funding Information: This research was supported by grants from the National Institutes of Health RO1HD067541 and P20GM121334 (BL, LA)/Office of Research, UMMC (BL) AHA 19CDA34670055 (LA) and AMAG-LUMARA Pharmaceutical Company (BL, LA). Funding Information: This research was supported by grants from the National Institutes of Health RO1HD067541 and P20GM121334 (BL, LA)/Office of Research, UMMC (BL) AHA 19CDA34670055 (LA) and AMAG-LUMARA Pharmaceutical Company (BL, LA). Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = oct,

doi = "10.1016/j.preghy.2020.09.002",

language = "English",

volume = "22",

pages = "151--155",

journal = "Pregnancy Hypertension",

issn = "2210-7789",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - 17-Hydroxyprogesterone caproate improves hypertension and renal endothelin-1 in response to sFlt-1 induced hypertension in pregnant rats

AU - Amaral, Lorena M.

AU - Cottrell, Jesse N.

AU - Comley, Kyleigh M.

AU - Cunningham, Mark W.

AU - Witcher, Alexis

AU - Vaka, Venkata Ramana

AU - Ibrahim, Tarek

AU - LaMarca, Babbette

N1 - Funding Information: This research was supported by grants from the National Institutes of Health RO1HD067541 and P20GM121334 (BL, LA)/Office of Research, UMMC (BL) AHA 19CDA34670055 (LA) and AMAG-LUMARA Pharmaceutical Company (BL, LA). Funding Information: This research was supported by grants from the National Institutes of Health RO1HD067541 and P20GM121334 (BL, LA)/Office of Research, UMMC (BL) AHA 19CDA34670055 (LA) and AMAG-LUMARA Pharmaceutical Company (BL, LA). Publisher Copyright: © 2020 The Author(s)

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

KW - 17-OHPC

KW - Preeclampsia

KW - Preproendothelin-1

KW - sFlt-1

UR - http://www.scopus.com/inward/record.url?scp=85091368507&partnerID=8YFLogxK

U2 - 10.1016/j.preghy.2020.09.002

DO - 10.1016/j.preghy.2020.09.002

M3 - Article

C2 - 32980622

AN - SCOPUS:85091368507

SN - 2210-7789

VL - 22

SP - 151

EP - 155

JO - Pregnancy Hypertension

JF - Pregnancy Hypertension

ER -

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

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Keywords

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