Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation.

Hypertension
Yongzhong WeiJ R Sowers

Abstract

Emerging evidence indicates that mineralocorticoid receptor (MR) blockade reduces the risk of cardiovascular events beyond those predicted by its blood pressure-lowering actions; however, the underlying mechanisms remain unclear. To investigate whether protection elicited by MR blockade is through attenuation of vascular apoptosis and injury, independently of blood pressure lowering, we administered a low dose of the MR antagonist spironolactone or vehicle for 21 days to hypertensive transgenic Ren2 rats with elevated plasma aldosterone levels. Although Ren2 rats developed higher systolic blood pressures compared with Sprague-Dawley littermates, low-dose spironolactone treatment did not reduce systolic blood pressure compared with untreated Ren2 rats. Ren2 rats exhibited vascular injury as evidenced by increased apoptosis, hemidesmosome-like structure loss, mitochondrial abnormalities, and lipid accumulation compared with Sprague-Dawley rats, and these abnormalities were attenuated by MR antagonism. Protein kinase B activation is critical to vascular homeostasis via regulation of cell survival and expression of apoptotic genes. Protein kinase B serine(473) phosphorylation was impaired in Ren2 aortas and restored with MR antagon...Continue Reading

References

May 1, 1995·Hypertension·D J CampbellS L Skinner
May 10, 2000·Nature Medicine·G Kroemer, J C Reed
Sep 16, 2000·Circulation Research·S Dimmeler, A M Zeiher
Feb 24, 2001·Basic Research in Cardiology·L RössigA M Zeiher
May 17, 2001·Current Hypertension Reports·C E Gomez-Sanchez, E P Gomez-Sanchez
Feb 14, 2002·The Journal of Biological Chemistry·Fuminori TsurutaYukiko Gotoh
Oct 18, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Ricardo RochaJohn A Delyani
Dec 31, 2002·Journal of Molecular and Cellular Cardiology·Noeleen De AngelisSerge Masson
Feb 28, 2004·Circulation Research·Isao ShiraishiMark A Sussman
Oct 29, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Vicenta Llorente-CortésLina Badimon
Jan 25, 2006·Hypertension·Ernesto L Schiffrin
Feb 21, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Wenyuan ZhaoYao Sun
Feb 25, 2006·Endocrinology·Tracy A WilliamsPaolo Mulatero
Sep 20, 2006·The Journal of Biological Chemistry·Yongzhong WeiCraig S Stump
Oct 20, 2006·Apoptosis : an International Journal on Programmed Cell Death·Søren Ulrik Salling SønderKlaus Bendtzen
Feb 22, 2007·The Journal of Biological Chemistry·Lin YangJin Q Cheng
Jun 26, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Shawna A CooperJames R Sowers
Aug 3, 2007·American Journal of Physiology. Renal Physiology·Hitesh PatniPravin C Singhal
Sep 6, 2007·American Journal of Nephrology·E M V de CavanaghL Ferder
Sep 29, 2007·Circulation Research·Xiaomei GuoRui-Ping Xiao
Dec 7, 2007·Cell Metabolism·Carlos Fernández-HernandoWilliam C Sessa
Jan 4, 2008·Hypertension·Nancy J Brown
Feb 26, 2008·Experimental Cell Research·Victor V PetrovPaul J Lijnen
Apr 9, 2008·Current Opinion in Hematology·Vyacheslav A Korshunov, Bradford C Berk
May 9, 2008·American Journal of Physiology. Renal Physiology·Jayant T MathewPravin C Singhal

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Citations

May 15, 2012·Current Hypertension Reports·Adam Whaley-Connell, James R Sowers
Jan 18, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Javad HabibiJames R Sowers
Mar 6, 2009·American Journal of Physiology. Renal Physiology·Adam Whaley-ConnellJames R Sowers
Dec 30, 2011·American Journal of Nephrology·Adam T Whaley-ConnellJames R Sowers
Jul 21, 2010·Hypertension·Srinivasa Raju Datla, Kathy K Griendling
Aug 21, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jun RenJames R Sowers
Jun 18, 2010·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yongji YanXu Zhang
Mar 17, 2010·Progress in Cardiovascular Diseases·Adam Whaley-ConnellJames R Sowers
Jun 11, 2010·Journal of the American Geriatrics Society·Philip A Kithas, Mark A Supiano
Nov 21, 2014·European Journal of Heart Failure·Mahmut AkpekAli Ergin
May 31, 2016·European Journal of Pharmacology·Jingwei GaoHui Huang
Dec 16, 2016·British Journal of Pharmacology·Ioannis AkoumianakisCharalambos Antoniades
Oct 23, 2014·The Journal of Endocrinology·Morag J Young, Amanda J Rickard
Apr 19, 2013·Hypertension·James R Sowers
May 19, 2010·Hypertension·Ralf P Brandes
Sep 5, 2009·Clinical Journal of the American Society of Nephrology : CJASN·Gaurav JainDavid G Warnock
Apr 8, 2020·International Journal of Hypertension·Nouralsalhin AlaagibMohammed Kardash
Sep 4, 2015·American Journal of Physiology. Renal Physiology·Narihito TatsumotoTakanari Kitazono
Oct 12, 2018·Cardiovascular Diabetology·Xiao-Yan QiZhi-Sheng Jiang
Mar 28, 2017·Kidney International·Adam Whaley-Connell, James R Sowers

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