Evidence map›Paper›PMID 21685445›Full record

ArticleExperimental physiology2011

Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke.

Adam P Mecca, Robert W Regenhardt, Timothy E O'Connor, Jason P Joseph, Mohan K Raizada, Michael J Katovich, Colin Sumners

Open access · bronzeAbstract read
In one paragraph

Article in Experimental physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 4 pooled it
8.8field-weighted citation impact, top 2% 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

102 citing papers in PubMed, 4 syntheses or guidelines pooled it, 193 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Cerebral ischemic and hemorrhagic complications of coronavirus disease 2019.International journal of stroke : official journal of the International Stroke Society · 2020
    Pooled it
  4. Renin-angiotensin system gene expression and neurodegenerative diseases.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016
    Pooled it
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. The Contribution of the Renin-Angiotensin System to Alzheimer's Disease.Current topics in behavioral neurosciences · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  18. Article
  19. Review
  20. Article

42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Adam P MeccaDepartment of Physiology & Functional Genomics, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0274, USA.
Robert W Regenhardt
Timothy E O'Connor
Jason P Joseph
Mohan K Raizada
Michael J Katovich
Colin Sumners
University of Florida · US

Funding

Multidisciplinary Training Program in HypertensionT32HL083810 · NHLBI · UNIVERSITY OF FLORIDA · PI WOOD, CHARLES E · 2007 to 2017
$2.5M
Vascular Reparative Mechanism by ACE2/Ang-(1-7)in DiabetesR01HL110170 · NHLBI · UNIVERSITY OF FLORIDA · PI GRANT, MARIA BARTOLOMEO · 2011 to 2015
$2.2M
NO Dysregulation of the Peripheral Clock in Diabetic ComplicationsR01DK090730 · NIDDK · UNIVERSITY OF FLORIDA · PI GRANT, MARIA BARTOLOMEO · 2010 to 2013
$1.3M
Cerebroprotection via viral-mediated gene delivery of angiotensin AT2 receptorsF30NS060335 · NINDS · UNIVERSITY OF FLORIDA · PI MECCA, ADAM PETER · 2008 to 2011
$141k
Howard Hughes Medical InstituteNHLBI NIH HHS R01 HL110170NHLBI NIH HHS T32 HL-083810NHLBI NIH HHS T32 HL083810NIDDK NIH HHS R01 DK090730NINDS NIH HHS F30 NS-060335NINDS NIH HHS F30 NS060335
6 · The paper itself

Abstract

Activation of angiotensin-converting enzyme 2 (ACE2), production of angiotensin-(1-7) [Ang-(1-7)] and stimulation of the Ang-(1-7) receptor Mas exert beneficial actions in various peripheral cardiovascular diseases, largely through opposition of the deleterious effects of angiotensin II via its type 1 receptor. Here we considered the possibility that Ang-(1-7) may exert beneficial effects against CNS damage and neurological deficits produced by cerebral ischaemic stroke. We determined the effects of central administration of Ang-(1-7) or pharmacological activation of ACE2 on the cerebral damage and behavioural deficits elicited by endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO), a model of cerebral ischaemia. The results of the present study demonstrated that intracerebroventricular infusion of either Ang-(1-7) or an ACE2 activator, diminazine aceturate (DIZE), prior to and following ET-1-induced MCAO significantly attenuated the cerebral infarct size and neurological deficits measured 72 h after the insult. These beneficial actions of Ang-(1-7) and DIZE were reversed by co-intracerebroventricular administration of the Mas receptor inhibitor, A-779. Neither the Ang-(1-7) nor the DIZE treatments altered the reduction in cerebral blood flow elicited by ET-1. Lastly, intracerebroventricular administration of Ang-(1-7) significantly reduced the increase in inducible nitric oxide synthase mRNA expression within the cerebral infarct that occurs following ET-1-induced MCAO. This is the first demonstration of cerebroprotective properties of the ACE2-Ang-(1-7)-Mas axis during ischaemic stroke, and suggests that the mechanism of the Ang-(1-7) protective action includes blunting of inducible nitric oxide synthase expression.

Indexed as

Angiotensin-Converting Enzyme 2Angiotensin IAngiotensin IIAnimalsDiminazeneEndothelin-1Enzyme ActivationInfarction, Middle Cerebral ArteryMaleNitric Oxide Synthase Type IIPeptide FragmentsPeptidyl-Dipeptidase AProto-Oncogene MasProto-Oncogene ProteinsRatsRats, Sprague-Dawley7-Ala-angiotensin (1-7)Ace2 protein, ratAngiotensin-Converting Enzyme 2Angiotensin Iangiotensin I (1-7)Angiotensin IIDiminazenediminazene aceturateEndothelin-1Nitric Oxide Synthase Type IINos2 protein, ratPeptide FragmentsPeptidyl-Dipeptidase AProto-Oncogene MasProto-Oncogene ProteinsReceptors, G-Protein-Coupled

Identifiers

PMID21685445
PMCPMC3210510
OpenAlexW1485797085

What OpenQuestion holds

Textmetadata
LicenceTDM
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.