Cardiomyocyte Mineralocorticoid Receptor Activation Impairs Acute Cardiac Functional Recovery After Ischemic Insult

Hypertension
Laura A BienvenuMorag J Young

Abstract

Loss of mineralocorticoid receptor signaling selectively in cardiomyocytes can ameliorate cardiac fibrotic and inflammatory responses caused by excess mineralocorticoids. The aim of this study was to characterize the role of cardiomyocyte mineralocorticoid receptor signaling in ischemia-reperfusion injury and recovery and to identify a role of mineralocorticoid receptor modulation of cardiac function. Wild-type and cardiomyocyte mineralocorticoid receptor knockout mice (8 weeks) were uninephrectomized and maintained on (1) high salt (0.9% NaCl, 0.4% KCl) or (2) high salt plus deoxycorticosterone pellet (0.3 mg/d, 0.9% NaCl, 0.4% KCl). After 8 weeks of treatment, hearts were isolated and subjected to 20 minutes of global ischemia plus 45 minutes of reperfusion. Mineralocorticoid excess increased peak contracture during ischemia regardless of genotype. Recovery of left ventricular developed pressure and rates of contraction and relaxation post ischemia-reperfusion were greater in knockout versus wild-type hearts. The incidence of arrhythmic activity during early reperfusion was significantly higher in wild-type than in knockout hearts. Levels of autophosphorylated Ca(2+)/calmodulin protein kinase II (Thr287) were elevated in hear...Continue Reading

References

Aug 3, 2002·Hypertension·John C BarbatoRoberto Franco-Saenz
May 10, 2007·Canadian Journal of Physiology and Pharmacology·Saori MatsuiHideharu Hayashi
Nov 28, 2007·Pflügers Archiv : European journal of physiology·Jean-Sébastien RougierHugues Abriel
Dec 2, 2008·Journal of Molecular and Cellular Cardiology·Richard D Vaughan-JonesPawel Swietach
Dec 23, 2009·Journal of Molecular and Cellular Cardiology·Martín Vila-PetroffAlicia Mattiazzi
Dec 24, 2009·European Heart Journal·Katharina SchmidtThomas Krieg
Jul 5, 2011·Clinical and Experimental Pharmacology & Physiology·James R BellLea Md Delbridge
Aug 9, 2011·Molecular and Cellular Endocrinology·Alex Odermatt, Denise V Kratschmar
Nov 15, 2011·Nature Medicine·B Julie HeMark E Anderson
Dec 7, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Dafina PruthiIris Z Jaffe
Jul 23, 2014·Endocrinology·Katelee Barrett MuellerIris Z Jaffe
Feb 25, 2015·Trends in Endocrinology and Metabolism : TEM·Yasir ParvizFaiez Zannad

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Citations

Jan 29, 2019·The Journal of Endocrinology·ELizabeth K FletcherMorag J Young
Aug 1, 2020·Journal of Human Hypertension·Morag J YoungJun Yang
Nov 19, 2020·Current Opinion in Pharmacology·Monica Kanki, Morag J Young
Aug 21, 2021·Essays in Biochemistry·Morag J Young, Colin D Clyne

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