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

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

doi:10.1016/j.preghy.2020.09.002

Cited by 8 publications

(3 citation statements)

References 47 publications

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“…Notably, IH-exposed pregnant and nonpregnant rats and mice exhibited heightened serum tumor necrosis factor- α (TNF α ) levels and soluble fms-like tyrosine kinase-1 (sFlt-1) [7, 8, 69]. Studies showed the infusion of TNF α and sFlt-1 into pregnant rats increased BP, augmented tissue levels of endothelin-1, and compromised endothelial function [70, 71]. It is worth exploring whether the release of these vasoactive factors during IH influences the expression and activity of endothelial ET B R.…”

Section: Discussionmentioning

confidence: 99%

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Song,

Yadav,

Dangudubiyyam

et al. 2023

Biology of Reproduction

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Obstructive sleep apnea (OSA) is a recognized risk factor for gestational hypertension, yet the exact mechanism behind this association remains unclear. Here, we tested the hypothesis that intermittent hypoxia (IH), a hallmark of OSA, induces gestational hypertension through perturbed endothelin-1 signaling. Pregnant Sprague–Dawley rats were subjected to normoxia (control), mild IH (mIH, 10.5% O2), or severe IH (sIH, 6.5% O2) from gestational day 10–21. Blood pressure (BP) was monitored. Plasma was collected and mesenteric arteries were isolated for myograph and protein analyses. The mIH and sIH groups demonstrated elevated BP, reduced plasma nitrate/nitrite (NOx), and unchanged endothelin-1 levels compared to the control group. Western blot analysis revealed decreased expression of endothelin type B receptor (ETBR) and phosphorylated endothelial nitric oxide synthase (eNOS), while the levels of endothelin type A receptor (ETAR) and total eNOS remained unchanged following IH exposure. The contractile responses to potassium chloride, phenylephrine, and endothelin-1 were unaffected in endothelium-denuded arteries from mIH and sIH rats. However, mIH and sIH rats exhibited impaired endothelium-dependent vasorelaxation responses to ETBR agonist IRL-1620 and acetylcholine compared to controls. Endothelium denudation abolished IRL-1620-induced vasorelaxation, supporting the involvement of endothelium in ETBR-mediated relaxation. Treatment with IRL-1620 during IH exposure significantly attenuated IH-induced hypertension in pregnant rats. This was associated with elevated circulating NOx levels, enhanced ETBR expression, increased eNOS activation, and improved vasodilation responses. Our data suggested that IH exposure during gestation increases BP in pregnant rats by suppressing ETBR-mediated signaling, providing a molecular mechanism linking IH and gestational hypertension.

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Section: Discussionmentioning

confidence: 99%

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Song,

Yadav,

Dangudubiyyam

et al. 2023

Biology of Reproduction

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“…Progesterone supplementation with progesterone derivatives such as 17-OHPC has long been used to decrease the risk of recurrent preterm labor. Anti-inflammatory effects and blood pressure reduction due to vasodilatation are considered to be the main actions [43].…”

Section: Hydroxyprogesterone Caproatementioning

confidence: 99%

Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide)

Takenoya,

Shibato,

Yamashita

et al. 2023

IJMS

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The aim of this research was to test the efficacy and potential clinical application of intranasal administration of galanin-like peptide (GALP) as an anti-obesity treatment under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed that, compared with a control (saline), intranasally administered GALP prevented further body weight gain in diet-induced obesity (DIO) mice with continued access to an HFD. Using an omics-based approach, we identified several genes and metabolites in the liver tissue of DIO mice that were altered by the administration of intranasal GALP. We used whole-genome DNA microarray and metabolomics analyses to determine the anti-obesity effects of intranasal GALP in DIO mice fed an HFD. Transcriptomic profiling revealed the upregulation of flavin-containing dimethylaniline monooxygenase 3 (Fmo3), metallothionein 1 and 2 (Mt1 and Mt2, respectively), and the Aldh1a3, Defa3, and Defa20 genes. Analysis using the DAVID tool showed that intranasal GALP enhanced gene expression related to fatty acid elongation and unsaturated fatty acid synthesis and downregulated gene expression related to lipid and cholesterol synthesis, fat absorption, bile uptake, and excretion. Metabolite analysis revealed increased levels of coenzyme Q10 and oleoylethanolamide in the liver tissue, increased levels of deoxycholic acid (DCA) and taurocholic acid (TCA) in the bile acids, increased levels of taurochenodeoxycholic acid (TCDCA), and decreased levels of ursodeoxycholic acid (UDCA). In conclusion, intranasal GALP administration alleviated weight gain in obese mice fed an HFD via mechanisms involving antioxidant, anti-inflammatory, and fatty acid metabolism effects and genetic alterations. The gene expression data are publicly available at NCBI GSE243376.

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“…10 Previous in-vitro studies concluded that the administration of 17-OHPC to preeclamptic rats decreased blood pressure, proteinuria, inflammation, TNF-α-induced hypertension, and improved vascular endothelial NO synthase expression in placenta. [11][12][13][14] This could improve the pregnancy outcomes due to placental ischemia, therefore addition of 17-OHPC should be considered for the management of early onset PE. Therefore, the present study aimed to evaluate the effect of 17-OHPC on IL-6 and TNF-α in expectantly managed early-onset PE.…”

Section: Introductionmentioning

confidence: 99%

Effect of 17-Hydroxyprogesterone Caproate on Interleukin-6 and Tumor necrosis factor-alpha in expectantly managed early-onset preeclampsia

Othman

Badawy

Sobh

et al. 2023

EJI

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The study aimed to evaluate the effect of 17 hydroxy progesterone (17-OHPC) on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in expectantly managed early-onset preeclampsia (PE). A randomized open-label controlled study included women who were diagnosed as early-onset PE if they assigned to expectant management according to the American College of Obstetricians and Gynecologists (ACOG) 2013 criteria for diagnosis of severity of PE. Patients were randomized into Group A (40 patients) received 17-OHPC 250 mg intra-muscular at admission and every 7 days thereafter and Group B (40 patients) was given the usual conservative measures of early-onset PE as a control group. Blood samples were obtained from all participants for measurements of TNF-α and IL-6 levels at admission and repeated at termination of pregnancy. The primary outcome was the mean difference between TNF-α and IL-6 levels before and after treatment in both groups. TNF-α and IL-6 levels at admission were not different between the two groups. However, there was a significant difference concerning these inflammatory biomarkers within the same group at admission and at termination (p<0.001), with significant decline of IL-6 and TNF-α level in the 17-OHPC treated group and significant rise of IL-6 and TNF-α in the control group. There was a strong positive correlation between systolic blood pressure (SBP) at admission and TNF-α level (r= 0.867, p=0.017), and moderately positive significant correlation between diastolic blood pressure (DBP) at admission and TNF-α (r=0.610, p<0.001). There was a mild positive significant correlation between IL-6 levels and SBP (r= 0.231, p=0.039), and DBP (r= 0.203, p= 0.041) at admission. In conclusion, 17–OHPC has no effect in improving maternal or neonatal outcomes in conservatively managed early onset PE, although it alters the inflammatory markers levels (IL-6 and TNF-α) that could improve the pathogenesis of PE.

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

Cited by 8 publications

References 47 publications

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide)

Effect of 17-Hydroxyprogesterone Caproate on Interleukin-6 and Tumor necrosis factor-alpha in expectantly managed early-onset preeclampsia

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