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Olmesartan attenuates the development of heart failure after experimental autoimmune myocarditis in rats through the modulation of ANG 1-7 mas receptor.
Mol Cell Endocrinol. 2012 Apr 04; 351(2):208-19.MC

Abstract

Angiotensin-converting enzyme 2 (ACE-2) is a membrane-associated carboxy-peptidase catalyzes the conversion of the vasoconstrictor angiotensin (ANG)-II to the vasodilatory peptide ANG 1-7. In view of the expanding axis of the renin angiotensin system, we have investigated the cardioprotective effects of olmesartan (10mg/kg/day) in experimental autoimmune myocarditis. Olmesartan treatment effectively suppressed the myocardial protein expressions of inflammatory markers in comparison to the vehicle-treated rats. However, the protein and mRNA levels of ACE-2 and ANG 1-7, and its receptor Mas were upregulated in olmesartan treated group compared to vehicle-treated rats. Olmesartan medoxomil treatment significantly decreased the expression levels of phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, phospho-ERK and phospho-(MAPK) activated protein kinase-2 than with those of vehicle-treated rats. Moreover, vehicle-treated rats were shown to be up-regulated protein expressions of NADPH oxidase subunits (p47phox, p67phox and Nox-4), myocardial apoptotic markers and endoplasmic reticulum stress markers in comparison to those of normal and all these effects are expectedly down-regulated by an olmesartan. In addition, attenuated protein levels of phosphatidylinositol-3-kinase (PI3K) and phospho-Akt in the vehicle-treated EAM rats were prevented by olmesartan treatment. Our results suggest that beneficial effects of olmesartan treatment was more effective therapy in combating the inflammation, oxidative stress, apoptosis and signaling pathways associated with heart failure at least in part via the modulation of ANG 1-7 mas receptor.

Authors+Show Affiliations

Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. svkumar1979@yahoo.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

22200414

Citation

Sukumaran, Vijayakumar, et al. "Olmesartan Attenuates the Development of Heart Failure After Experimental Autoimmune Myocarditis in Rats Through the Modulation of ANG 1-7 Mas Receptor." Molecular and Cellular Endocrinology, vol. 351, no. 2, 2012, pp. 208-19.
Sukumaran V, Veeraveedu PT, Gurusamy N, et al. Olmesartan attenuates the development of heart failure after experimental autoimmune myocarditis in rats through the modulation of ANG 1-7 mas receptor. Mol Cell Endocrinol. 2012;351(2):208-19.
Sukumaran, V., Veeraveedu, P. T., Gurusamy, N., Lakshmanan, A. P., Yamaguchi, K., Ma, M., Suzuki, K., Nagata, M., Takagi, R., Kodama, M., & Watanabe, K. (2012). Olmesartan attenuates the development of heart failure after experimental autoimmune myocarditis in rats through the modulation of ANG 1-7 mas receptor. Molecular and Cellular Endocrinology, 351(2), 208-19. https://doi.org/10.1016/j.mce.2011.12.010
Sukumaran V, et al. Olmesartan Attenuates the Development of Heart Failure After Experimental Autoimmune Myocarditis in Rats Through the Modulation of ANG 1-7 Mas Receptor. Mol Cell Endocrinol. 2012 Apr 4;351(2):208-19. PubMed PMID: 22200414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Olmesartan attenuates the development of heart failure after experimental autoimmune myocarditis in rats through the modulation of ANG 1-7 mas receptor. AU - Sukumaran,Vijayakumar, AU - Veeraveedu,Punniyakoti T, AU - Gurusamy,Narasimman, AU - Lakshmanan,Arun Prasath, AU - Yamaguchi,Ken'ichi, AU - Ma,Meilei, AU - Suzuki,Kenji, AU - Nagata,Masaki, AU - Takagi,Ritsuo, AU - Kodama,Makoto, AU - Watanabe,Kenichi, Y1 - 2011/12/19/ PY - 2011/06/02/received PY - 2011/12/09/revised PY - 2011/12/12/accepted PY - 2011/12/28/entrez PY - 2011/12/28/pubmed PY - 2012/10/10/medline SP - 208 EP - 19 JF - Molecular and cellular endocrinology JO - Mol Cell Endocrinol VL - 351 IS - 2 N2 - Angiotensin-converting enzyme 2 (ACE-2) is a membrane-associated carboxy-peptidase catalyzes the conversion of the vasoconstrictor angiotensin (ANG)-II to the vasodilatory peptide ANG 1-7. In view of the expanding axis of the renin angiotensin system, we have investigated the cardioprotective effects of olmesartan (10mg/kg/day) in experimental autoimmune myocarditis. Olmesartan treatment effectively suppressed the myocardial protein expressions of inflammatory markers in comparison to the vehicle-treated rats. However, the protein and mRNA levels of ACE-2 and ANG 1-7, and its receptor Mas were upregulated in olmesartan treated group compared to vehicle-treated rats. Olmesartan medoxomil treatment significantly decreased the expression levels of phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, phospho-ERK and phospho-(MAPK) activated protein kinase-2 than with those of vehicle-treated rats. Moreover, vehicle-treated rats were shown to be up-regulated protein expressions of NADPH oxidase subunits (p47phox, p67phox and Nox-4), myocardial apoptotic markers and endoplasmic reticulum stress markers in comparison to those of normal and all these effects are expectedly down-regulated by an olmesartan. In addition, attenuated protein levels of phosphatidylinositol-3-kinase (PI3K) and phospho-Akt in the vehicle-treated EAM rats were prevented by olmesartan treatment. Our results suggest that beneficial effects of olmesartan treatment was more effective therapy in combating the inflammation, oxidative stress, apoptosis and signaling pathways associated with heart failure at least in part via the modulation of ANG 1-7 mas receptor. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/22200414/Olmesartan_attenuates_the_development_of_heart_failure_after_experimental_autoimmune_myocarditis_in_rats_through_the_modulation_of_ANG_1_7_mas_receptor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(11)00734-9 DB - PRIME DP - Unbound Medicine ER -