Show simple item record

dc.contributor.authorIravanian, Shahriar
dc.contributor.authorSovari, Ali A.
dc.contributor.authorLardin, Harvey A.
dc.contributor.authorLiu, Hong
dc.contributor.authorXiao, Hong D.
dc.contributor.authorDolmatova, Elena
dc.contributor.authorJiao, Zhe
dc.contributor.authorHarris, Brett S.
dc.contributor.authorWitham, Emily A.
dc.contributor.authorGourdie, Robert G.
dc.contributor.authorDuffy, Heather S.
dc.contributor.authorBernstein, Kenneth E.
dc.contributor.authorDudley Jr., Samuel C.
dc.date.accessioned2012-03-21T15:28:48Z
dc.date.available2012-03-21T15:28:48Z
dc.date.issued2011-07
dc.identifier.bibliographicCitationIravanian, S., Sovari, A. A., Lardin, H. A., Liu, H., Xiao, H. D., Dolmatova, E., Jiao, Z., Harris, B. S., Witham, E. A., Gourdie, R. G., Duffy, H. S., Bernstein, K. E., & Dudley, J. 2011. Inhibition of renin-angiotensin system (RAS) reduces ventricular tachycardia risk by altering connexin43. Journal of Molecular Medicine, 89(7): 677-687. DOI: 10.1007/s00109-011-0761-3en
dc.identifier.issn0946-2716
dc.identifier.otherDOI: 10.1007/s00109-011-0761-3
dc.identifier.urihttp://hdl.handle.net/10027/8244
dc.descriptionPost print version of article may differ from published version. The original publication is available at springerlink.com; DOI: 10.1007/s00109-011-0761-3.en
dc.description.abstractAims: Renin-angiotensin system (RAS) activation is associated with arrhythmias. We investigated the effects of RAS inhibition in cardiac-specific angiotensin converting enzyme (ACE) overexpression (ACE 8/8) mice, which exhibit proclivity to ventricular tachycardia (VT) and sudden death because of reduced connexin43 (Cx43). Methods and Results: ACE 8/8 mice were treated with an ACE inhibitor (captopril) or an angiotensin receptor type-1 blocker (losartan). Subsequently, electrophysiological studies were performed, and the hearts were extracted for Cx43 quantification using immunoblotting, immunohistochemistry, fluorescent dye spread method and sodium current quantification using whole cell patch clamping. VT was induced in 12.5% of captopril treated ACE 8/8 and in 28.6% of losartan treated mice, compared to 87.5% of untreated mice (P<0.01). Losartan and captopril treatment increased total Cx43 2.4-fold (P=0.01) and the Cx43 phosphorylation ratio 2.3-fold (P=0.005). Treatment was associated with a recovery of gap junctional conductance. Survival in treated mice improved to 0.78 at 10 weeks (95% confidence interval 0.64 to 0.92), compared to the expected survival of less than 0.50. Conclusions: In a model of RAS activation, arrhythmic risk was correlated with reduced Cx43 amount and phosphorylation. RAS inhibition resulted in increased total and phosphorylated Cx43, decreased VT inducibility, and improved survival.en
dc.language.isoen_USen
dc.publisherSpringer Verlagen
dc.titleInhibition of Renin-Angiotensin System (RAS) Reduces Ventricular Tachycardia Risk by Altering Connexin43en
dc.typeArticleen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record