HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Am J Physiol Heart Circ Physiol 292: H912-H920, 2007. First published September 29, 2006; doi:10.1152/ajpheart.00824.2006
0363-6135/07 $8.00

This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 292/2/H912    most recent 00824.2006v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Yaras, N. Articles by Turan, B. Search for Related Content PubMed PubMed Citation Articles by Yaras, N. Articles by Turan, B.

Restoration of diabetes-induced abnormal local Ca²⁺ release in cardiomyocytes by angiotensin II receptor blockade

¹Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey; and ²Institut National de la Santé et de la Recherche Médicale, Physiopathologie Cardiovasculaire, Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, France

Submitted 1 August 2006 ; accepted in final form 19 September 2006

Stimulation of local renin-angiotensin system and increased levels of oxidants characterize the diabetic heart. Downregulation of ANG II type 1 receptors (AT₁) and enhancement in PKC activity in the heart point out the role of AT₁ blockers in diabetes. The purpose of this study was to evaluate a potential role of an AT₁ blocker, candesartan, on abnormal Ca²⁺ release mechanisms and its relationship with PKC in the cardiomyocytes from streptozotocin-induced diabetic rats. Cardiomyocytes were isolated enzymatically and then incubated with either candesartan or a nonspecific PKC inhibitor bisindolylmaleimide I (BIM) for 6–8 h at 37°C. Both candesartan and BIM applied on diabetic cardiomyocytes significantly restored the altered kinetic parameters of Ca²⁺ transients, as well as depressed Ca²⁺ loading of sarcoplasmic reticulum, basal Ca²⁺ level, and spatiotemporal properties of the Ca²⁺ sparks. In addition, candesartan and BIM significantly antagonized the hyperphosphorylation of cardiac ryanodine receptor (RyR2) and restored the depleted protein levels of both RyR2 and FK506 binding protein 12.6 (FKBP12.6). Furthermore, candesartan and BIM also reduced the increased PKC levels and oxidized protein thiol level in membrane fraction of diabetic rat cardiomyocytes. Taken together, these data demonstrate that AT₁ receptor blockade protects cardiomyocytes from development of cellular alterations typically associated with Ca²⁺ release mechanisms in diabetes mellitus. Prevention of these alterations by candesartan may present a useful pharmacological strategy for the treatment of diabetic cardiomyopathy.

heart; candesartan; Type 1 diabetes; thiol oxidation

This article has been cited by other articles:

				H. Cheng and W. J. Lederer Calcium Sparks Physiol Rev, October 1, 2008; 88(4): 1491 - 1545. [Abstract] [Full Text] [PDF]

				G. Zhou, X. Li, D. W. Hein, X. Xiang, J. P. Marshall, S. D. Prabhu, and L. Cai Metallothionein Suppresses Angiotensin II-Induced Nicotinamide Adenine Dinucleotide Phosphate Oxidase Activation, Nitrosative Stress, Apoptosis, and Pathological Remodeling in the Diabetic Heart J. Am. Coll. Cardiol., August 19, 2008; 52(8): 655 - 666. [Abstract] [Full Text] [PDF]

				N. Yaras, E. Tuncay, N. Purali, B. Sahinoglu, G. Vassort, and B. Turan Sex-related effects on diabetes-induced alterations in calcium release in the rat heart Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3584 - H3592. [Abstract] [Full Text] [PDF]

				S. Boudina and E. D. Abel Diabetic Cardiomyopathy Revisited Circulation, June 26, 2007; 115(25): 3213 - 3223. [Abstract] [Full Text] [PDF]