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Citations to this article

Cardiac mast cell–derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion
Christina J. Mackins, … , Randi B. Silver, Roberto Levi
Christina J. Mackins, … , Randi B. Silver, Roberto Levi
Published April 3, 2006
Citation Information: J Clin Invest. 2006;116(4):1063-1070. https://doi.org/10.1172/JCI25713.
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Research Article Cardiology Article has an altmetric score of 4

Cardiac mast cell–derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion

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Abstract

Having identified renin in cardiac mast cells, we assessed whether its release leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I–forming activity. This activity was blocked by the selective renin inhibitor BILA2157, indicating that renin was responsible for Ang I formation. Local generation of cardiac Ang II from mast cell–derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT1) receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea pig and mouse hearts, a significant coronary spillover of renin and norepinephrine was observed. In both models, this was accompanied by ventricular fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly reduced active renin overflow and attenuated both norepinephrine release and arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated with BILA2157 or the AT1 receptor antagonist EXP3174. Renin overflow and arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast cell–deficient mice than in control hearts. Thus, mast cell–derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion. Mast cell–derived renin may be a useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias, sudden cardiac death, myocardial ischemia, and congestive heart failure.

Authors

Christina J. Mackins, Seiichiro Kano, Nahid Seyedi, Ulrich Schäfer, Alicia C. Reid, Takuji Machida, Randi B. Silver, Roberto Levi

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 2 2 3 3 2 5 7 2 2 3 8 5 3 10 8 7 7 4 1 84
Citation information
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Citations to this article in year 2017 (2)

Title and authors Publication Year
Bidirectional Mast Cell–Eosinophil Interactions in Inflammatory Disorders and Cancer
MR Galdiero, G Varricchi, M Seaf, G Marone, F Levi-Schaffer, G Marone
Frontiers in Medicine 2017
S1P receptor 1-Mediated Anti–Renin-Angiotensin System Cardioprotection: Pivotal Role of Mast Cell Aldehyde Dehydrogenase Type 2
A Marino, T Sakamoto, PA Robador, K Tomita, R Levi
The Journal of pharmacology and experimental therapeutics 2017

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