Brain angiotensin-converting enzymes: role of angiotensin-converting enzyme 2 in processing angiotensin II in mice

dc.creatorElased, KM
dc.creatorCunha, TS
dc.creatorMarcondes, FK
dc.creatorMorris, M
dc.date2008
dc.dateMAY 1
dc.date2014-11-14T21:26:39Z
dc.date2015-11-26T17:16:56Z
dc.date2014-11-14T21:26:39Z
dc.date2015-11-26T17:16:56Z
dc.date.accessioned2018-03-29T00:05:05Z
dc.date.available2018-03-29T00:05:05Z
dc.identifierExperimental Physiology. Wiley-blackwell, v. 93, n. 5, n. 665, n. 675, 2008.
dc.identifier0958-0670
dc.identifierWOS:000255286000019
dc.identifier10.1113/expphysiol.2007.040311
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/78247
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/78247
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/78247
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1282391
dc.descriptionAngiotensin (Ang)-converting enzyme 2 (ACE2) metabolizes Ang II to the vasodilatory peptide Ang(1-7), while neprilysin (NEP) generates Ang(1-7) from Ang I. Experiments used novel Surface Enhanced Laser Desorption Ionization-Time of Flight (SELDI-TOF) mass spectroscopic (MS) assays to study Ang processing. Mass spectroscopy was used to measure proteolytic conversion of Ang peptide substrates to their specific peptide products. We compared ACE/ACE2 activity in plasma, brain and kidney from C57BL/6 and NEP(-/-) mice. Plasma or tissue extracts were incubated with Ang I or Ang II (1296 or 1045, m/z, respectively), and generated peptides were monitored with MS. Angiotensin-converting enzyme 2 activity was detected in kidney and brain, but not in plasma. Brain ACE2 activity was highest in hypothalamus. Angiotensin-converting enzyme 2 activity was inhibited by the specific ACE2 inhibitor, DX600 (10 mu M, 99% inhibition), but not by the ACE inhibitor, captopril (10 mu M). Both MS and colorimetric assays showed high ACE activity in plasma and kidney with low levels in brain. To extend these findings, ACE measurements were made in ACE overexpressing mice. Angiotensin-converting enzyme four-copy mice showed higher ACE activity in kidney and plasma with low levels in hypothalamus. In hypothalamus from NEP(-/-) mice, generation of Ang(1-7) from Ang I was decreased, suggesting a role for NEP in Ang metabolism. With Ang II as substrate, there was no difference between NEP(-/-) and wild-type control mice, indicating that other enzymes may contribute to generation of Ang(1-7). The data suggest a predominant role of hypothalamic ACE2 in the processing of Ang II, in contrast to ACE, which is most active in plasma.
dc.description93
dc.description5
dc.description665
dc.description675
dc.languageen
dc.publisherWiley-blackwell
dc.publisherMalden
dc.publisherEUA
dc.relationExperimental Physiology
dc.relationExp. Physiol.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectSpontaneously Hypertensive-rats
dc.subjectNucleus-tractus-solitarii
dc.subjectMessenger-rna
dc.subjectProlyl Endopeptidase
dc.subjectSystem
dc.subjectAce2
dc.subjectExpression
dc.subjectNeprilysin
dc.subjectReceptor
dc.subjectHomolog
dc.titleBrain angiotensin-converting enzymes: role of angiotensin-converting enzyme 2 in processing angiotensin II in mice
dc.typeArtículos de revistas


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