Evidence map›Paper›PMID 33739377›Full record

ArticleBiology of reproduction2021

Activation of angiotensin type 2 receptor attenuates testosterone-induced hypertension and uterine vascular resistance in pregnant rats†.

Jay S Mishra, Sathish Kumar

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of reproduction, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
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  4. Reduced ATHypertension (Dallas, Tex. : 1979) · 2025
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  18. The Angiotensin ATPharmacological reviews · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Jay S MishraDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
Sathish KumarDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
University of Wisconsin–Madison · US

Funding

Sex-specific fetal programming of adult vascular dysfunction and hypertensionR01HL119869 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI KUMAR, SATHISH · 2013 to 2017
$1.9M
Vascular AT2R expression and function during pregnancyR01HL134779 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI KUMAR, SATHISH · 2017 to 2020
$1.5M
National Institute of Health HL134779NHLBI NIH HHS R01 HL119869NHLBI NIH HHS R01 HL134779
6 · The paper itself

Abstract

Preeclampsia is a pregnancy-related hypertensive disorder with unclear mechanisms. While hypersensitivity to angiotensin II via vasoconstrictive angiotensin type-1 receptor (AT1R) is observed in preeclampsia, the importance of vasodilatory angiotensin type-2 receptor (AT2R) in the control of vascular dysfunction is less clear. We assessed whether AT1R, AT2R, and endothelial nitric oxide synthase (eNOS) expression are altered in placental vessels of preeclamptic women and tested if ex vivo incubation with AT2R agonist Compound 21 (C21; 1 μM) could restore AT1R, AT2R, and eNOS balance. Further, using a rat model of gestational hypertension induced by elevated testosterone, we examined whether C21 (1 μg/kg/day, oral) could preserve AT1R and AT2R balance and improve blood pressure, uterine artery blood flow, and vascular function. Western blots revealed that AT1R protein level was higher while AT2R and eNOS protein were reduced in preeclamptic placental vessels, and AT2R agonist C21 decreased AT1R and increased AT2R and eNOS protein levels in preeclamptic vessels. In testosterone dams, blood pressure was higher, and uterine artery blood flow was reduced, and C21 treatment reversed these levels similar to those in controls dams. C21 attenuated the exaggerated Ang II contraction and improved endothelium-dependent vasorelaxation in uterine arteries of testosterone dams. These C21-mediated vascular effects were associated with decreased AT1R and increased AT2R and eNOS protein levels. C21 also increased serum nitrate/nitrite and bradykinin production in testosterone dams and attenuated the fetoplacental growth restriction. Thus, AT1R upregulation and AT2R downregulation are observed in preeclampsia and testosterone model, and increasing AT2R activity could help restore AT1R and AT2R balance and improve gestational vascular function.

Indexed as

AdultAnimalsFemaleHumansHypertensionNitric Oxide Synthase Type IIIRatsRats, Sprague-DawleyReceptor, Angiotensin, Type 1Receptor, Angiotensin, Type 2TestosteroneUterusVascular ResistanceYoung AdultAgtr1a protein, ratAgtr2 protein, ratNitric Oxide Synthase Type IIINos3 protein, ratReceptor, Angiotensin, Type 1Receptor, Angiotensin, Type 2TestosteroneangiotensinAT2 receptorsblood flowendotheliumfetuspreeclampsiapregnancytestosteronevascular function

Identifiers

PMID33739377
PMCPMC8660162
OpenAlexW3136858356

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.