Skip to main content

Advertisement

SpringerLink
Log in

Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar–Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 μg/kg/min Ang II for 14 days. The Ang II + ANP and ANP rats also received 0.1 μg/kg/min ANP intravenously. The Ang II and Ang II + ANP rats showed comparable blood pressure. Left ventricular fractional shortening and ejection fraction were lower in the Ang II rats than in controls; these indices were higher (P < 0.001) in the Ang II + ANP rats than in the Ang II rats. In the Ang II rats, the peak velocity of mitral early inflow and its ratio to atrial contraction-related peak flow velocity were lower, and the deceleration time of mitral early inflow was significantly prolonged; these changes were decreased by ANP. Percent fibrosis was higher (P < 0.001) and average myocyte diameters greater (P < 0.01) in the Ang II rats than in controls. ANP decreased both myocardial fibrosis (P < 0.01) and myocyte hypertrophy (P < 0.01). Macrophage infiltration, expression of mRNA levels of collagen types I and III, monocyte chemotactic protein-1, and a profibrotic/proinflammatory molecule, tenascin-C (TN-C) were increased in the Ang II rats; ANP significantly decreased these changes. In vitro, Ang II increased expression of TN-C and endothelin-1 (ET-1) in cardiac fibroblasts, which were reduced by ANP. ET-1 upregulated TN-C expression via endothelin type A receptor. These results suggest that ANP may protect the heart from Ang II-induced remodeling by attenuating inflammation, at least partly through endothelin 1/endothelin receptor A cascade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Levin ER, Gardner DG, Samson WK (1998) Natriuretic peptides. N Engl J Med 339:321–328

    Article  PubMed  CAS  Google Scholar 

  2. Schultz HD, Gardner DG, Deschepper CF, Coleridge HM, Coleridge JC (1998) Vagal C-fiber blockade abolishes sympathetic inhibition by atrial natriuretic factor. Am J Physiol 255:R6–R13

    Google Scholar 

  3. Ehara S, Nakamura Y, Matsumoto K, Hasegawa T, Shimada K, Takagi M, Hanatani A, Izumi Y, Terashima M, Yoshiyama M (2012) Effects of intravenous atrial natriuretic peptide and nitroglycerin on coronary vasodilation and flow velocity determined using 3 T magnetic resonance imaging in patients with nonischemic heart failure. Heart Vessels. doi:10.1007/s00380-012-0292-z

    Google Scholar 

  4. Kasamaki Y, Izumi Y, Ozawa Y, Ohta M, Tano A, Watanabe I, Hirayama A, Nakayama T, Kawamura H, Himit D, Mahemuti M, Sezai A (2012) Relationship between status of plasma atrial natriuretic peptide and heart rate variability in human subjects. Heart Vessels. doi:10.1007/s00380-012-0237-6

    PubMed  Google Scholar 

  5. Kasama S, Furuya M, Toyama T, Ichikawa S, Kurabayashi M (2008) Effect of atrial natriuretic peptide on left ventricular remodeling in patients with acute myocardial infarction. Eur Heart J 29:1485–1494

    Article  PubMed  CAS  Google Scholar 

  6. Saito Y (2010) Roles of atrial natriuretic peptide and its therapeutic use. J Cardiol 56:262–270

    Article  PubMed  Google Scholar 

  7. Ishikawa C, Tsutamoto M, Wada A, Fujii M, Ohno K, Sakai H, Yamamoto T, Horie M (2005) Inhibition of aldosterone and endothelin-1 by carperitide was attenuated with more than 1 week of infusion in patients with congestive heart failure. J Cardiovasc Pharmacol 46:513–518

    Article  PubMed  CAS  Google Scholar 

  8. Tanaka T, Tsutamoto T, Sakai H, Nishiyama K, Fujii M, Yamamoto T, Horie M (2008) Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail 10:360–366

    Article  PubMed  CAS  Google Scholar 

  9. Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A, Okazaki H, Asai M, Nagamachi Y, Maeda N, Shintani Y, Minamino T, Asakura M, Kishimoto I, Funahashi T, Tomoike H, Kitakaze M (2009) Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol 53:2070–2077

    Article  PubMed  CAS  Google Scholar 

  10. Hattori H, Minami Y, Mizuno M, Yumino D, Hoshi H, Arashi H, Nuki T, Sashida Y, Higashitani M, Serizawa N, Yamada N, Yamaguchi J, Mori F, Shiga T, Hagiwara N (2012) Differences in hemodynamic responses between intravenous carperitide and nicorandil in patients with acute heart failure syndromes. Heart Vessels. doi:1007/s00380-012-0252-7

    PubMed  Google Scholar 

  11. Yamaji M, Tsutamoto T, Tanaka T, Kawahara C, Nishiyama K, Yamamoto T, Fujii M, Horie M (2009) Effect of carperitide on plasma adiponectin levels in acute decompensated heart failure patients with diabetes mellitus. Circ J 73:2264–2269

    Article  PubMed  CAS  Google Scholar 

  12. Nomura F, Kurobe N, Mori Y, Hikita A, Kawai M, Suwa M, Okutani Y (2008) Multicenter prospective investigation on efficacy and safety of carperitide as a first-line drug for acute heart failure syndrome with preserved blood pressure: COMPASS: carperitide effects observed through monitoring dyspnea in acute decompensated heart failure study. Circ J 72:1777–1786

    Article  PubMed  CAS  Google Scholar 

  13. Hata N, Seino Y, Tsutamoto T, Hiramitsu S, Kaneko N, Yoshikawa T, Yokoyama H, Tanaka K, Mizuno K, Nejima J, Kinoshita M (2008) Effects of carperitide on the long-term prognosis of patients with acute decompensated chronic heart failure: the PROTECT multicenter randomized controlled study. Circ J 72:1787–1793

    Article  PubMed  CAS  Google Scholar 

  14. Kuga H, Ogawa K, Oida A, Taguchi I, Nakatsugawa M, Hoshi T, Sugimura H, Abe S, Kaneko A (2003) Administration of atrial natriuretic peptide attenuates reperfusion phenomena and preserves left ventricular regional wall motion after direct coronary angioplasty for acute myocardial infarction. Circ J 67:443–448

    Article  PubMed  CAS  Google Scholar 

  15. Kasama S, Toyama T, Hatori T, Sumino H, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M (2007) Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with first anterior acute myocardial infarction. J Am Coll Cardiol 49:667–674

    Article  PubMed  CAS  Google Scholar 

  16. Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, Seguchi O, Myoishi M, Minamino T, Ohara T, Nagai Y, Nanto S, Watanabe K, Fukuzawa S, Hirayama A, Nakamura N, Kimura K, Fujii K, Ishihara M, Saito Y, Tomoike H, Kitamura S; J-WIND investigators (2007) Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet 370:1483–1493

  17. Hayashi M, Tsutamoto T, Wada A, Maeda K, Mabuchi N, Tsutsui T, Horie M, Ohnishi M, Kinoshita M (2001) Intravenous atrial natriuretic peptide prevents left ventricular remodeling in patients with first anterior acute myocardial infarction. J Am Coll Cardiol 37:1820–1826

    Article  PubMed  CAS  Google Scholar 

  18. Tsuneyoshi H, Nishina T, Nomoto T, Kanemitsu H, Kawakami R, Unimonh O, Nishimura K, Komeda M (2004) Atrial natriuretic peptide helps prevent late remodeling after left ventricular aneurysm repair. Circulation 110:II174–II179

    Google Scholar 

  19. Tanaka K, Ito M, Kodama M, Hoyano M, Kimura S, Mitsuwa W, Hirono S, Adachi T, Watanabe K, Nakazawa M, Aizawa Y (2009) Long-term carperitide treatment attenuates left ventricular remodeling in rats with heart failure after autoimmune myocarditis. J Cardiovasc Pharmacol 54:232–239

    Article  PubMed  CAS  Google Scholar 

  20. Fiebeler A, Nussberger J, Shagdarsuren E, Rong S, Hilfenhaus G, Al-Saadi N, Dechend R, Wellner M, Meiners S, Maser-Gluth C, Jeng AY, Webb RL, Luft FC, Muller DN (2005) Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage. Circulation 111:3087–3094

    Article  PubMed  CAS  Google Scholar 

  21. Kuwahara F, Kai H, Tokuda K, Takeya M, Takeshita A, Egashira K, Imaizumi T (2004) Hypertensive myocardial fibrosis and diastolic dysfunction: another model of inflammation? Hypertension 43:739–745

    Article  PubMed  CAS  Google Scholar 

  22. Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, McMahon EG, Delyani JA (2004) Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol 283:H1802–H1810

    Google Scholar 

  23. Endemann DH, Touyz RM, Iglarz M, Savoia C, Schiffrin EL (2004) Eplerenone prevents salt induced vascular remodeling and cardiac fibrosis in stroke-prone spontaneously hypertensive rats. Hypertension 43:1252–1257

    Article  PubMed  CAS  Google Scholar 

  24. Frangogiannis NG, Shimoni S, Chang SM, Ren G, Dewald O, Gersch C, Shan K, Aggeli C, Reardon M, Letsou GV, Espada R, Ramchandani M, Entman ML, Zoghbi WA (2002) Active interstitial remodeling: an important process in the hibernating human myocardium. J Am Coll Cardiol 39:1468–1474

    Article  PubMed  Google Scholar 

  25. Imanaka-Yoshida K, Hiroe M, Yasutomi Y, Toyozaki T, Tsuchiya T, Noda N, Maki T, Nishikawa T, Sakakura T, Yoshida T (2002) Tenascin-C is a useful marker for disease activity in myocarditis. J Pathol 197:388–394

    Article  PubMed  CAS  Google Scholar 

  26. Imanaka-Yoshida K, Matsumoto K, Hara M, Sakakura T, Yoshida T (2003) The dynamic expression of tenascin-C and tenascin-X during early heart development in the mouse. Differentiation 71:291–298

    Article  PubMed  CAS  Google Scholar 

  27. Morimoto S, Imanaka-Yoshida K, Hiramitsu S, Kato S, Ohtsuki M, Uemura A, Kato Y, Nishikawa T, Toyozaki T, Hishida H, Yoshida T, Hiroe M (2005) Diagnostic utility of tenascin-C for evaluation of the activity of human acute myocarditis. J Pathol 205:460–467

    Article  PubMed  CAS  Google Scholar 

  28. Nishioka T, Suzuki M, Onishi K, Takakura N, Inada H, Yoshida T, Hiroe M, Imanaka-Yoshida K (2007) Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse: involvement of tenascin-C induced by aldosterone-mediated inflammation. J Cardiovasc Pharmacol 49:261–268

    Article  PubMed  CAS  Google Scholar 

  29. Tamura A, Kusachi S, Nogami K, Yamanishi A, Kajikawa Y, Hirohata S, Tsuji T (1996) Tenascin expression in endomyocardial biopsy specimens in patients with dilated cardiomyopathy: distribution along margin of fibrotic lesions. Heart 75:291–294

    Article  PubMed  CAS  Google Scholar 

  30. Tsukada B, Terasaki F, Shimomura H, Otsuka K, Otsuka K, Katashima T, Fujita S, Imanaka-Yoshida K, Yoshida T, Hiroe M, Kitaura Y (2009) High prevalence of chronic myocarditis in dilated cardiomyopathy referred for left ventriculoplasty: expression of tenascin-C as a possible marker for inflammation. Human Pathol 40:1015–1022

    Article  CAS  Google Scholar 

  31. Okamoto H, Imanaka-Yoshida K (2012) Matricellular proteins: new molecular targets to prevent heart failure. Cardiovasc Ther 30:198–209

    Article  Google Scholar 

  32. Imanaka-Yoshida K (2012) Tenascin-C in cardiovascular tissue remodeling. From development to inflammation and repair. Circ J 76:2513–2520

    Article  PubMed  CAS  Google Scholar 

  33. Imanaka-Yoshida K, Hiroe M, Nishikawa T, Ishiyama S, Shimojo T, Ohta Y, Sakakura T, Yoshida T (2001) Tenascin-C modulates adhesion of cardiomyocytes to extracellular matrix during tissue remodeling after myocardial infarction. Lab Invest 81:1015–1024

    Article  PubMed  CAS  Google Scholar 

  34. Tamaoki M, Imanaka-Yoshida K, Yokoyama K, Nishioka T, Inada H, Hiroe M, Sakakura T, Yoshida T (2005) Tenascin-C regulates recruitment of myofibroblasts during tissue repair after myocardial injury. Am J Pathol 167:71–80

    Article  PubMed  CAS  Google Scholar 

  35. Calderone A, Thaik CM, Takahashi N, Chang DL, Colucci WS (1998) Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. J Clin Invest 101:812–818

    Article  PubMed  CAS  Google Scholar 

  36. Hayashi D, Kudoh S, Shiojima I, Zou Y, Harada K, Shimoyama M, Imai Y, Monzen K, Yamazaki T, Yazaki Y, Nagai R, Komuro I (2004) Atrial natriuretic peptide inhibits cardiomyocyte hypertrophy through mitogen-activated protein kinase phosphatase-1. Biochem Biophys Res Commun 322:310–319

    Article  PubMed  CAS  Google Scholar 

  37. Holtwick R, van Eickels M, Skryabin BV, Baba HA, Bubikat A, Begrow F, Schneider MD, Garbers DL, Kuhn M (2003) Pressure-independent cardiac hypertrophy in mice with cardiomyocyte-restricted inactivation of the atrial natriuretic peptide receptor guanylyl cyclase-A. J Clin Invest 111:1399–1407

    PubMed  CAS  Google Scholar 

  38. Oliver PM, Fox JE, Kim R, Rockman HA, Kim HS, Reddick RL, Pandey KN, Milgram SL, Smithies O, Maeda N (1997) Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. Proc Natl Acad Sci USA 94:14730–14735

    Article  PubMed  CAS  Google Scholar 

  39. Knowles JW, Esposito G, Mao L, Hagaman JR, Fox JE, Smithies O, Rockman HA, Maeda N (2001) Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice. J Clin Invest 107:975–984

    Article  PubMed  CAS  Google Scholar 

  40. Kishimoto I, Rossi K, Garbers DL (2001) A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy. Proc Natl Acad Sci USA 98:2703–2706

    Article  PubMed  CAS  Google Scholar 

  41. Manabe I (2011) Chronic inflammation links cardiovascular, metabolic and renal diseases. Circ J 75:2739–2748

    Article  PubMed  CAS  Google Scholar 

  42. Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NG (2010) The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. J Mol Cell Cardiol 48:504–511

    Article  PubMed  CAS  Google Scholar 

  43. Bornstein P (1995) Diversity of function is inherent in matricellular proteins: an appraisal of thrombospondin 1. J Cell Biol 130:503–506

    Article  PubMed  CAS  Google Scholar 

  44. Bornstein P, Sage EH (2002) Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol 14:608–616

    Article  PubMed  CAS  Google Scholar 

  45. Midwood KS, Hussenet T, Langlois B, Orend G (2011) Advances in tenascin-C biology. Cell Mol Life Sci 68:3175–3199

    Article  PubMed  CAS  Google Scholar 

  46. Chiquet-Ehrismann R, Tucker RP (2011) Tenascins and the importance of adhesion modulation. Cold Spring Harb Perspect Biol 3

  47. Kanayama M, Morimoto J, Matsui Y, Ikesue M, Danzaki K, Kurotaki D, Ito K, Yoshida T, Uede T (2011) α9β1 integrin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cell generation. J Immunol 187:5851–5864

    Article  PubMed  CAS  Google Scholar 

  48. Udalova IA, Ruhmann M, Thomson SJ, Midwood KS (2011) Expression and immune function of tenascin-C. Crit Rev Immunol 31:115–145

    Article  PubMed  CAS  Google Scholar 

  49. El-Karef A, Yoshida T, Gabazza EC, Nishioka T, Inada H, Sakakura T, Imanaka-Yoshida K (2007) Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis in mice. J Pathol 211:86–94

    Article  PubMed  CAS  Google Scholar 

  50. Midwood K, Sacre S, Piccinini AM, Inglis J, Trebaul A, Chan E, Drexler S, Sofat N, Kashiwagi M, Orend G, Brennan F, Foxwell B (2009) Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med 15:774–780

    Article  PubMed  CAS  Google Scholar 

  51. Nishioka T, Onishi K, Shimojo N, Nagano Y, Matsusaka H, Ikeuchi M, Ide T, Tsutsui H, Hiroe M, Yoshida T, Imanaka-Yoshida K (2010) Tenascin-C may aggravate left ventricular remodeling and function after myocardial infarction in mice. Am J Physiol Heart Circ Physiol 298:H1072–H1078

    Article  PubMed  CAS  Google Scholar 

  52. Moriyama N, Taniguchi M, Miyano K, Miyoshi M, Watanabe T (2006) ANP inhibits LPS-induced stimulation of rat microglial cells by suppressing NF-kappaB and AP-1 activations. Biochem Biophys Res Commun 350:322–328

    Article  PubMed  CAS  Google Scholar 

  53. Ladetzki-Baehs K, Keller M, Kiemer AK, Koch E, Zahler S, Wendel A, Vollmar AM (2007) Atrial natriuretic peptide, a regulator of nuclear factor-kappa B activation in vivo. Endocrinology 148:332–336

    Article  PubMed  CAS  Google Scholar 

  54. Kiemer AK, Hartung T, Vollmar AM (2000) cGMP-mediated inhibition of TNF-alpha production by the atrial natriuretic peptide in murine macrophages. J Immunol 165:175–181

    PubMed  CAS  Google Scholar 

  55. Leask A (2010) Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ Res 106:1675–1680

    Article  PubMed  CAS  Google Scholar 

  56. Fujisaki H, Ito H, Hirata Y, Tanaka M, Hata M, Lin M, Adachi S, Akimoto H, Marumo F, Hiroe M (1995) Natriuretic peptides inhibit angiotensin II-induced proliferation of rat cardiac fibroblasts by blocking endothelin-1 gene expression. J Clin Invest 96:1059–1065

    Article  PubMed  CAS  Google Scholar 

  57. Glenn DJ, Rahmutula D, Nishimito M, Liang F, Gardner DG (2009) Atrial natriuretic peptide suppresses endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4-dependent mechanism. Cardiovasc Res 84:209–217

    Article  PubMed  CAS  Google Scholar 

  58. Lange K, Kammerer M, Hegi ME, Grotegut S, Dittmann A, Huang W, Fluri E, Yip GW, Gotte M, Ruiz C, Orend G (2007) Endothelin receptor type B counteracts tenascin-C-induced endothelin receptor type A-dependent focal adhesion and actin stress fiber disorganization. Cancer Res 67:6163–6173

    Article  PubMed  CAS  Google Scholar 

  59. Nagaharu K, Zhang X, Yoshida T, Katoh D, Hanamura N, Kozuka Y, Ogawa T, Shiraishi T, Imanaka-Yoshida K (2011) Tenascin C induces epithelial-mesenchymal transition-like change accompanied by SRC activation and focal adhesion kinase phosphorylation in human breast cancer cells. Am J Pathol 178:754–763

    Article  PubMed  CAS  Google Scholar 

  60. Ishigaki T, Imanaka-Yoshida K, Shimojo N, Matsushima S, Taki W, Yoshida T (2011) Tenascin-C enhances crosstalk signaling of integrin αvβ3/PDGFR-β complex by SRC recruitment promoting PDGF-induced proliferation and migration in smooth muscle cells. J Cell Physiol 226:2617–2624

    Article  PubMed  CAS  Google Scholar 

  61. Ito H, Hirata Y, Hiroe M, Tsujino M, Adachi S, Takamoto T, Nitta M, Taniguchi K, Marumo F (1991) Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes. Circ Res 69:209–215

    Article  PubMed  CAS  Google Scholar 

  62. Ito H, Hirata Y, Adachi S, Tanaka M, Tsujino M, Koike A, Nogami A, Marumo F, Hiroe M (1993) Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin Il-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest 92:398–403

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank M. Namikata for providing technical assistance, and also thank Dr Y. Ito (Division of Life Sciences, Department of Anatomy and Cell Biology, Osaka Medical College) for her excellent advice on confocal laser scanning microscopy, and A. Yamaki (ASUBIO Pharma Co., Ltd) for helpful discussion on the protocol design. This work was supported by JSPS Grants-in-Aid for Scientific Research #21590927(to K. I-Y.), and a research grant for intractable diseases from the Ministry of Health, Labor and Welfare of Japan (to K. I-Y. and Y. K.). Part of the study was also supported by a grant by Daiichi-Sankyo Co. Ltd.

Author information

Authors and Affiliations

  1. Department of Cardiology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan

    Shuichi Fujita, Naoshi Shimojo, Fumio Terasaki, Kaoru Otsuka, Yasushi Kitaura & Nobukazu Ishizaka

  2. Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Naoshi Shimojo, Tomohiro Nishioka, Toshimichi Yoshida & Kyoko Imanaka-Yoshida

  3. Mie University Research Center for Matrix Biology, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Naoshi Shimojo, Toshimichi Yoshida & Kyoko Imanaka-Yoshida

  4. Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan

    Noriko Hosotani & Yuka Kohda

  5. Department of Nursing Science, Baika Women’s University, 2-19-5 Shukunosho, Ibaraki, Osaka, 567-8578, Japan

    Takao Tanaka

  6. Department of Cardiology, National Center of Global Health and Medicine, 1-2-1Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan

    Michiaki Hiroe

Authors
  1. Shuichi Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoshi Shimojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fumio Terasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaoru Otsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noriko Hosotani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuka Kohda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takao Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tomohiro Nishioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Toshimichi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michiaki Hiroe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yasushi Kitaura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Nobukazu Ishizaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kyoko Imanaka-Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Nobukazu Ishizaka or Kyoko Imanaka-Yoshida.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fujita, S., Shimojo, N., Terasaki, F. et al. Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade. Heart Vessels 28, 646–657 (2013). https://doi.org/10.1007/s00380-012-0311-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-012-0311-0

Keywords

Search

Navigation