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Beneficial effects of olmesartan, a novel angiotensin II receptor type 1 antagonist, upon acute autoimmune myocarditis

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Abstract

Excess amount of cytokine produced by inflammatory stimuli contributes to the progression of myocardial damage in myocarditis. Some angiotensin II receptor type 1 antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. We tested the hypothesis that olmesartan, a novel angiotensin II receptor type 1 antagonist, ameliorated experimental autoimmune myocarditis (EAM) in rats attributing to the suppression of inflammatory cytokines in the heart. We orally administered olmesartan 1, 3, and 10 mg/kg/day to rats with EAM for 3 weeks. The results showed that olmesartan decreased blood pressure significantly compared with the untreated group, but markedly reduced the severity of myocarditis by comparing the heart weight/body weight ratio, pericardial effusion scores, macroscopic scores and microscopic scores. Myocardial interleukin (IL)-1β expression by western blotting and IL-1β-positive staining cells by immunohistochemistry were significantly lower in rats with EAM given olmesartan treatment compared with those of rats given vehicle. We conclude that Olmesartan ameliorates acute EAM in rats. The cardioprotection of olmesartan may be due to suppression of inflammatory cytokines dependent of the hemodynamic modifications.

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References

  1. Kawai C: From myocarditis to cardiomyopathy: Mechanisms of inflammation and cell death. Circulation 99: 1091-1100, 1999

    PubMed  Google Scholar 

  2. Kodama M, Matsumoto Y, Fujiwara M, Masani F, Izumi T, Shibata A: A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol 57: 250-262, 1990

    Article  PubMed  Google Scholar 

  3. Stuehr DJ, Marletta MA: Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-γ. J Immunol 139: 518-525, 1987

    PubMed  Google Scholar 

  4. Adams V, Nehrhoff B, Spate U, Linke A, Schulze PC, Baur A, Gielen S, Hambrecht R, Schuler G: Induction of iNOS expression in skeletal muscle by IL-1beta and NF-kappaB activation: An in vitro and in vivo study. Cardiovasc Res 54: 95-104, 2002

    Article  PubMed  Google Scholar 

  5. Song W, Lu X, Feng Q: Tumor necrosis factor-alpha induces apoptosis via inducible nitric oxide synthase in neonatal mouse cardiomyocytes. Cardiovasc Res 45: 595-602, 2000

    Article  PubMed  Google Scholar 

  6. Mulligan MS, Hevel JM, Marletta MA, Ward PA: Tissue injury caused by deposition of immune complexes in L-arginine dependent. Proc Natl Acad Sci USA 88: 6338-6342, 1991

    PubMed  Google Scholar 

  7. Ishiyama S, Hiroe M, Nishikawa T, Abe S, Shimojo T, Ito H, Ozasa S, Yamakawa K, Matsuzaki M, Mohammed MU, Nakazawa H, Kasajima T, Marumo F: Nitric oxide contributes the progression of myocardial damage in experimental autoimmune myocarditis in rats. Circulation 95: 489-496, 1997

    PubMed  Google Scholar 

  8. Mungrue IN, Gros R, Pirani A, Azard A, Csont T, Schulz R, Butany J, Stewart DJ, Husain M: Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block, and sudden death. J Clin Invest 109: 735-743, 2002

    Article  PubMed  Google Scholar 

  9. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL: Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257: 387-389, 1992

    PubMed  Google Scholar 

  10. Furukawa T, Kobuke K, Matsumori A: Role of cytokines in autoimmune myocarditis and cardiomyopathy. Autoimmunity 34: 165-168, 2001

    PubMed  Google Scholar 

  11. Iwasaki A, Matsumori A, Yamada T, Shioi T, Wang W, Ono K, Nishio R, Okada M, Sasayama S: Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis: A possible mechanism through inhibition of nitric oxide production. J Am Coll Cardiol 33: 1400-1407, 1999

    Article  PubMed  Google Scholar 

  12. Mollnau H, Wendt M, Szöcs K, Lassèque B, Schulz E, Oelze M, Li H, Bodenschatz M, August M, Kleschyov AL, Tsilimingas N, Walter U, Förstermann U, Meinertz T, Griendling K, Münzel T: Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res 90: e58-e65, 2002

    Article  PubMed  Google Scholar 

  13. Warnholtz A, Nickering G, Schultz E, Macharzina R, Bräsen JH, Skatchkov M, Heiter T, Stasch JP, Griendling KK, Harrison DG, Böhm M, Meinertz T, Münzel T: Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis. Evidence for involvement of the renin-angiotensin system. Circulation 99: 2027-2033, 1999

    PubMed  Google Scholar 

  14. Burnier M: Angiotensin II type 1 receptor blockers. Circulation 103: 904-912, 2001

    PubMed  Google Scholar 

  15. Shioji K, Kishimoto C, Sasayama S: Fc receptor-mediated inhibitory effect of immunoglobulin therapy on autoimmune giant cell myocarditis: Concomitant suppression of the expression of dendritic cells. Circ Res 89: 540-546, 2001

    PubMed  Google Scholar 

  16. Matsumori A, Yamada T, Suzuki H, Matoba Y, Sasayama S: Increased circulating cytokines in patients with myocarditis and cardiomyopathy. Br Heart J 72: 561-566, 1994

    PubMed  Google Scholar 

  17. Shioi T, Matsumori A, Sasayama S: Persistent expression of cytokines in the chronic stage of viral myocarditis in mice. Circulation 94: 2930-2937, 1996

    PubMed  Google Scholar 

  18. Kubota T, McTiernan CF, Frye CS, Demetris AJ, Feldman AM: Cardiac-specific overexpression of tumor necrosis factor-alpha causes lethal myocarditis in transgenic mice. J Card Fail 3: 117-124, 1997

    Article  PubMed  Google Scholar 

  19. Lane JR, Neumann DA, Lafond-Walker A, Herskowitz A, Rose NR: Interleukin 1 or tumor necrosis factor can promote Coxsackie virus-induced myocarditis in resistant B10.A mice. J Exp Med 175: 1123-1123, 1992

    Article  PubMed  Google Scholar 

  20. Kishimoto C, Takada H, Kawamata H, Umatake M, Ochiai H: Immunoglobulin treatment prevents congestive heart failure in murine encephalomyocarditis viral myocarditis associated with reduction of inflammatory cytokines. J Pharmacol Exp Ther 299: 645-651, 2001

    PubMed  Google Scholar 

  21. Baruch L, Anand I, Cohen IS, Ziesche S, Judd D, Cohn JN: Augumented short-and long-term hemodynamic and hormonal effects of an angiotensin receptor blocker added to an angiotensin converting enzyme inhibitor therapy in patients with heart failure. Vasodilator Heart Failure Trial (V-HeFT) study group. Circulation 99: 2658-2664, 1999

    PubMed  Google Scholar 

  22. Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, Konstam MA, Riegger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B: Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure. Randomised trial. The Losartan Heart Failure Survival Study ELITE II. Lancet 355: 1582-1587, 2000

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan

    Masaomi Nimata, Chiharu Kishimoto, Zuyi Yuan & Keisuke Shioji

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  1. Masaomi Nimata
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  2. Chiharu Kishimoto
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  3. Zuyi Yuan
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  4. Keisuke Shioji
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Nimata, M., Kishimoto, C., Yuan, Z. et al. Beneficial effects of olmesartan, a novel angiotensin II receptor type 1 antagonist, upon acute autoimmune myocarditis. Mol Cell Biochem 259, 217–222 (2004). https://doi.org/10.1023/B:MCBI.0000021379.82282.53

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  • DOI: https://doi.org/10.1023/B:MCBI.0000021379.82282.53

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