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Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis.
Toxicology. 2012 Jan 27; 291(1-3):139-45.T

Abstract

Candesartan cilexetil, an angiotensin (Ang) II receptor 1 blocker was reported to suppress the myocardial damage in various cardiovascular complications but the mode by which it is effective in preventing the progression of dilated cardiomyopathy (DCM) is unknown. Emerging evidences suggest that, at least, part of the benefits observed with the use of AT1 receptor blockers could be attributed to the increased Ang (1-7) levels observed during administration of these agents. Identification of the novel components of the RAS, ACE2 and Ang (1-7) receptor mas, provided essential elements for considering the existence of a vasodilator arm of the RAS, represented by the ACE2-Ang (1-7)-mas axis. In this study, rat model of DCM was prepared by injection with porcine cardiac myosin. Twenty-eight days after immunization, candesartan cilexetil was administered intraperitoneally at 1 or 10mg/kg/day to rats for four weeks. Myocardial expression of Ang receptors and markers of calcium homeostasis, endoplasmic reticulum (ER) stress and apoptosis were measured by Western blotting and histopathological staining techniques. Candesartan improved the functional markers in a dose-dependent manner and also upregulated Ang (1-7), ACE2 and mas1 in the myocardium of DCM rats. Various ER stress and apoptosis markers were attenuated and the number apoptotic cells were significantly lower in the candesartan treated rats compared with those of the vehicle group. These findings suggest that candesartan treatment prevented the progression of DCM by activation of the counter regulatory arm of the RAS and possibly through modulation of ER stress and subsequently, cardiac apoptosis.

Authors+Show Affiliations

Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan. somasundaram143@rediffmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22120037

Citation

Arumugam, Somasundaram, et al. "Candesartan Cilexetil Protects From Cardiac Myosin Induced Cardiotoxicity Via Reduction of Endoplasmic Reticulum Stress and Apoptosis in Rats: Involvement of ACE2-Ang (1-7)-mas Axis." Toxicology, vol. 291, no. 1-3, 2012, pp. 139-45.
Arumugam S, Thandavarayan RA, Palaniyandi SS, et al. Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis. Toxicology. 2012;291(1-3):139-45.
Arumugam, S., Thandavarayan, R. A., Palaniyandi, S. S., Giridharan, V. V., Arozal, W., Sari, F. R., Soetikno, V., Harima, M., Suzuki, K., Kodama, M., & Watanabe, K. (2012). Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis. Toxicology, 291(1-3), 139-45. https://doi.org/10.1016/j.tox.2011.11.008
Arumugam S, et al. Candesartan Cilexetil Protects From Cardiac Myosin Induced Cardiotoxicity Via Reduction of Endoplasmic Reticulum Stress and Apoptosis in Rats: Involvement of ACE2-Ang (1-7)-mas Axis. Toxicology. 2012 Jan 27;291(1-3):139-45. PubMed PMID: 22120037.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis. AU - Arumugam,Somasundaram, AU - Thandavarayan,Rajarajan A, AU - Palaniyandi,Suresh S, AU - Giridharan,Vijayasree V, AU - Arozal,Wawaimuli, AU - Sari,Flori R, AU - Soetikno,Vivian, AU - Harima,Meilei, AU - Suzuki,Kenji, AU - Kodama,Makoto, AU - Watanabe,Kenichi, Y1 - 2011/11/23/ PY - 2011/10/08/received PY - 2011/11/12/revised PY - 2011/11/14/accepted PY - 2011/11/29/entrez PY - 2011/11/29/pubmed PY - 2012/2/7/medline SP - 139 EP - 45 JF - Toxicology JO - Toxicology VL - 291 IS - 1-3 N2 - Candesartan cilexetil, an angiotensin (Ang) II receptor 1 blocker was reported to suppress the myocardial damage in various cardiovascular complications but the mode by which it is effective in preventing the progression of dilated cardiomyopathy (DCM) is unknown. Emerging evidences suggest that, at least, part of the benefits observed with the use of AT1 receptor blockers could be attributed to the increased Ang (1-7) levels observed during administration of these agents. Identification of the novel components of the RAS, ACE2 and Ang (1-7) receptor mas, provided essential elements for considering the existence of a vasodilator arm of the RAS, represented by the ACE2-Ang (1-7)-mas axis. In this study, rat model of DCM was prepared by injection with porcine cardiac myosin. Twenty-eight days after immunization, candesartan cilexetil was administered intraperitoneally at 1 or 10mg/kg/day to rats for four weeks. Myocardial expression of Ang receptors and markers of calcium homeostasis, endoplasmic reticulum (ER) stress and apoptosis were measured by Western blotting and histopathological staining techniques. Candesartan improved the functional markers in a dose-dependent manner and also upregulated Ang (1-7), ACE2 and mas1 in the myocardium of DCM rats. Various ER stress and apoptosis markers were attenuated and the number apoptotic cells were significantly lower in the candesartan treated rats compared with those of the vehicle group. These findings suggest that candesartan treatment prevented the progression of DCM by activation of the counter regulatory arm of the RAS and possibly through modulation of ER stress and subsequently, cardiac apoptosis. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/22120037/Candesartan_cilexetil_protects_from_cardiac_myosin_induced_cardiotoxicity_via_reduction_of_endoplasmic_reticulum_stress_and_apoptosis_in_rats:_involvement_of_ACE2_Ang__1_7__mas_axis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(11)00491-4 DB - PRIME DP - Unbound Medicine ER -