ArticleCirculation research2013
Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 3 of them syntheses that pooled it.
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Who cites it
115 citing papers in PubMed, 3 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- Ischemic stroke associated with COVID-19: a systematic review and meta-analysis.Journal of neurology · 2022Pooled it
- Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.EBioMedicine · 2020Pooled it
- Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review.Annals of internal medicine · 2020Pooled it
- Proximal tubule ACE2 mediates early responses to hypertension by regulating intrarenal RAS and sodium homeostasis.JCI insight · 2026Article
- Sex-Specific Exosome Cargo Reveals Potential New Mechanisms of Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- ADAM17 Supports Disinhibition of Pre-sympathetic Glutamatergic Neurons Through Microglial Chemotaxis.Neuroscience bulletin · 2026Article
- Article
- Salt-sensitive hypertension promotes neuronal mitochondrial stress and neurodegenerative alterations via neuro-vascular metabolic reprogramming and local RAS signaling.Journal of neuroinflammation · 2025Article
- Central nervous system mechanisms of salt-sensitive hypertension.Physiological reviews · 2025Review
- Targeting Kinin B1R Attenuates Hypertension Through AT1R-Dependent Mechanisms.Circulation research · 2025Article
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023.Hypertension (Dallas, Tex. : 1979) · 2025Article
- UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Angiotensin-Converting Enzyme 2 Posttranslational Modifications and Implications for Hypertension and SARS-CoV-2: 2023 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Review
- SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.International journal of molecular sciences · 2024Article
- Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Maternal Western diet programs cardiometabolic dysfunction and hypothalamic inflammation via epigenetic mechanisms predominantly in the male offspring.Molecular metabolism · 2024Article
- Bridging metabolic syndrome and cognitive dysfunction: role of astrocytes.Frontiers in endocrinology · 2024Review
- Cardiovascular dysfunction induced by combined exposure to nicotine inhalation and high-fat diet.American journal of physiology. Heart and circulatory physiology · 2024Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
rationaleOveractivity of the brain renin-angiotensin system is a major contributor to neurogenic hypertension. Although overexpression of angiotensin-converting enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming angiotensin II into angiotensin-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension.
objectiveWe hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. METHODS AND
resultsTo test this hypothesis, we used the deoxycorticosterone acetate-salt model of neurogenic hypertension in nontransgenic and syn-hACE2 mice overexpressing ACE2 in neurons. Deoxycorticosterone acetate-salt treatment in nontransgenic mice led to significant increases in blood pressure, hypothalamic angiotensin II levels, inflammation, impaired baroreflex sensitivity, and autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, although these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled an increase in ACE2 activity in the cerebrospinal fluid of nontransgenic mice after deoxycorticosterone acetate-salt treatment and were accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function.
conclusionsOur data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension.
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Registered trials
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