ArticleBiology of reproduction2018
Pregnancy upregulates angiotensin type 2 receptor expression and increases blood flow in uterine arteries of rats.
Article in Biology of reproduction, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Maternal kidney adaptation and function in pregnancy: review and perspectives.Function (Oxford, England) · 2026Review
- Testosterone reduces uterine contractions in vivo: Evidence for non-genomic action in rats.PloS one · 2026Article
- The multifactorial role of HDAC9 at the maternal-fetal interface in the pathogenesis of preeclampsia.Clinical science (London, England : 1979) · 2025Review
- Reductions in angiotensin II type 2 receptor-mediated vasodilation contribute to increased angiotensin II vasoconstrictor sensitivity in women with preeclampsia history.Clinical science (London, England : 1979) · 2025Article
- Reduced ATHypertension (Dallas, Tex. : 1979) · 2025Article
- Per- and polyfluoroalkyl substances (PFAS) and hypertensive disorders of Pregnancy- integration of epidemiological and mechanistic evidence.Reproductive toxicology (Elmsford, N.Y.) · 2024Review
- H2S donor GYY4137 mitigates sFlt-1-induced hypertension and vascular dysfunction in pregnant rats†.Biology of reproduction · 2024Article
- Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.Comprehensive Physiology · 2024Review
- Stimulation of Angiotensin II Receptor Subtype 2 Reduces Preeclampsia-like Symptoms in a Mouse Model of Preeclampsia.Current issues in molecular biology · 2024Article
- Vasopressin and cardiovascular autonomic adjustment in chronic hypertensive pregnancy.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy.Frontiers in physiology · 2024Review
- Synergistic regulation of uterine radial artery adaptation to pregnancy by paracrine and hemodynamic factors.American journal of physiology. Heart and circulatory physiology · 2023Article
- Activation of the Renin-Angiotensin-Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy.International journal of molecular sciences · 2023Article
- Maternal perfluorooctane sulfonic acid exposure during rat pregnancy causes hypersensitivity to angiotensin II and attenuation of endothelium-dependent vasodilation in the uterine arteries †.Biology of reproduction · 2022Article
- The Angiotensin ATPharmacological reviews · 2022Review
- Maternal Nanomaterial Inhalation Exposure: Critical Gestational Period in the Uterine Microcirculation is Angiotensin II Dependent.Cardiovascular toxicology · 2022Article
- AT2R activation increases in vitro angiogenesis in pregnant human uterine artery endothelial cells.PloS one · 2022Article
- Role of the Uteroplacental Renin-Angiotensin System in Placental Development and Function, and Its Implication in the Preeclampsia Pathogenesis.Biomedicines · 2021Review
- Role of ACE2 in pregnancy and potential implications for COVID-19 susceptibility.Clinical science (London, England : 1979) · 2021Review
- Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation.International journal of molecular sciences · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Normal pregnancy is associated with decreased uterine vascular contraction and increased blood flow even though angiotensin II (AngII) levels are increased. AngII not only activates the angiotensin type 1 receptor (AT1R) to mediate vasoconstriction but also angiotensin type 2 receptor (AT2R) to cause vasodilation. We hypothesized that upregulation of AT2R expression and function accounts for increased uterine artery blood flow during pregnancy. Virgin, pregnant (at different days of gestation) and post-partum Sprague-Dawley rats were used to determine uterine artery hemodynamics using micro ultrasound and plasma angiotensin II levels by ELISA. Isolated uterine arteries were examined for AT1R and AT2R expression and isometric contraction/relaxation. Plasma AngII levels were steady up to mid-pregnancy, increased as pregnancy advanced, reaching a peak in late pregnancy, and then restored to pre-pregnant levels after delivery. The pattern of increase in AngII levels mirrored a parallel increase in uterine blood flow. AT1R expression did not change, but AT2R expression increased during pregnancy correlating with uterine blood flow increase. Treatment with the AT2R antagonist PD123319 reduced uterine arterial blood flow. Vasoconstriction to angiotensin II was blunted in pregnant rats. Treatment with PD123319 caused greater enhancement of AngII contraction in pregnant than virgin rats. Ex vivo exposure of estradiol to uterine arterial rings dose dependently upregulated AT2R expression, that was inhibited by estrogen receptor antagonist. These results demonstrate that elevated AngII levels during gestation induce an increase in uterine blood flow via heightened AT2R-mediated signaling. Estrogens appear to directly upregulate uterine vascular AT2R independent of any endogenous factors.
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