Linked Life Data

21059353

Source:http://linkedlifedata.com/resource/pubmed/id/21059353

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-10
pubmed:abstractText
Renin-angiotensin system inhibitors significantly reduce the incidence of arrhythmias. However, the underlying mechanism(s) is not well understood. We aim to test the hypothesis that angiotensin II (Ang II) induces early afterdepolarizations (EADs) and triggered activities (TAs) via the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-ROS-calmodulin kinase II (CaMKII) pathway. ROS production was analyzed in the isolated rabbit myocytes loaded with ROS dye. Ang II (1-2 ?M) increased ROS fluorescence in myocytes, which was abolished by Ang II type 1 receptor blocker losartan, NADPH oxidase inhibitor apocynin, and antioxidant MnTMPyP, respectively. Action potentials were recorded using the perforated patch-clamp technique. EADs emerged in 27 out of 41 (66%) cells at 15.8 ± 1.6 min after Ang II (1-2 ?M) perfusion. Ang II-induced EADs were eliminated by losartan, apocynin, or trolox. The CaMKII inhibitor KN-93 (n=6) and inhibitory peptide (AIP) (n=4) also suppressed Ang II-induced EADs, whereas the inactive analogue KN-92 did not. Nifedipine, a blocker of L-type Ca current (I(Ca)(2+)(,L)), or ranolazine, an inhibitor of late Na current (I(Na)(+)), abolished Ang II-induced EADs. The effects of Ang II on major membrane currents were evaluated using voltage clamp. While Ang II at same concentrations had no significant effect on total outward K(+) current, it enhanced I(Ca.L) and late I(Na), which were attenuated by losartan, apocynin, trolox, or KN-93. We conclude that Ang II induces EADs via intracellular ROS production through NADPH oxidase, activation of CaMKII, and enhancement of I(Ca,L) and late I(Na). These results provide evidence supporting a link between renin-angiotensin system and cardiac arrhythmias.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1095-8584
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
128-36
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Angiotensin II induces afterdepolarizations via reactive oxygen species and calmodulin kinase II signaling.
pubmed:affiliation
Department of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07101, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural