Skip to main content
SpringerLink
Log in

Reciprocal change in angiotensinogen mRNA expression in rat myocardium and liver after myocardial infarction

  • Originals
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Summary

The aim of this study was to analyze sequential change of angiotensinogen (Ao) mRNA expression in rat liver and noninfarcted myocardium after myocardial infarction (MI). Female sprague-Dawley rats were subjected either to left coronary artery occlusion or sham operation. Three weeks after MI, coronary artery ligation resulted in comparable infarct sizes. A hypokinetic thin anterior wall and remarkable dilatation of the left ventricle, as well as decreased contractility (left ventricular end-systslic dimension =6.0±0.4, 3.3±0.2, LV end-diastolic dimension =7.9±0.3, 5.9±0.2 mm, and fractional shortening =25.3±3.1%, 45.1±3.3%) were shown in the MI and sham group, respectively, by echocardiography (P<0.01). Experimental MI caused a significant fall in systolic blood pressure (MI 90±5.0, vs sham 130±7.5 mmHg;P<0.01) and significantly higher left ventricular end-diastolic pressure (MI 21±1.5, vs sham 11±1.0 mmHg;P<0.01). At 4, 18, and 24h after MI, liver Ao mRNA levels, as shown by Northern blot analysis, had increased by up to four times (Ao/glyceraldehyde-3-phosphate dehydrogenase (GAPDH)=1.4±0.1 and 6.0±0.2 at baseline and 4h after MI, respectively (P<0.01). After sham surgery, however, the corresponding increase was slight (maximal 1.5-fold). Three days after MI, liver mRNA had returned to the baseline level. In contrast, ATG mRNA expression in noninfarcted myocardium, as shown by reverse transcription-polymerase chain reaction and Southern blotting, decreased transiently during the acute phase. It returned to its baseline level within 3 days, and then increased further (Ao/ GAPDH=2.9±0.6, 0.3±0.1, 3.2±0.8, and 3.7±0.8 at baseline, 24h, 3 days, and 3 weeks after MI, respectively). In conclusion, it can be stated that after MI, the Ao gene contributes, acutely in the liver and chronically in the myocardium, to the maintenance of hemodynamic homeostasis during the acute phase and ventricular remodeling during the chronic phase.

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

Similar content being viewed by others

References

  1. Dzau VJ, Colucci WS, Hollenberg NK, Williams GH (1981) Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure. Circulation 63(3):645–651

    CAS  PubMed  Google Scholar 

  2. Dzau VJ (1993) Tissue renin-angiotensin system in myocardial hypertrophy and failure. Arch Intern Med 153:937–942

    Article  CAS  PubMed  Google Scholar 

  3. Pfeffer JM, Pfeffer MA, Braunwald E (1985) Influence of chronic captopril therapy on the infarcted left ventricle of rat. Circ Res 57:84–95

    CAS  PubMed  Google Scholar 

  4. Schieffer B, Wirger A., Meybrunn M, Seitz S, Holtz J, Riede UN, Drexler H (1994) Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation 89:2273–2282

    CAS  PubMed  Google Scholar 

  5. Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E (1988) Effects of captopril on progressive left ventricular dilatation after anterior myocardial infarction. N Engl J Med 319:80–86

    Article  CAS  PubMed  Google Scholar 

  6. Sharpe N, Murphy J, Smith H, Hannan S (1988) Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet 1:255–259

    Article  CAS  PubMed  Google Scholar 

  7. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC on behalf of the SAVE investigators (1992) Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial. N Engl J Med 327:667–677

    Article  Google Scholar 

  8. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group (1995) ISIS-4: A randomized factorial trial assesing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial infarction. Lancet 18:669–685

    Article  Google Scholar 

  9. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators (1993) Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 342:821–828

    Google Scholar 

  10. GISSI-3 (Gruppo Italiano per I1 Studio della Sopravvivenza nell’infarto Miocardico) Study Group (1994) GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 343:1115–1122

    Google Scholar 

  11. Fukamizu A, Takahashi S, Seo MS, Tada M, Tanimoto K, Uehara S, Murakami K (1990) Structure and expression of the human angiotensinogen gene. J Biol Chem 265:776–7582

    Google Scholar 

  12. Kageyama R, Ohkubo H, Nakanishi S (1985) Induction of rat liver angiotensinogen mRNA following acute inflammation. Biochem Biophys Res Commun 129:826–832

    Article  CAS  PubMed  Google Scholar 

  13. Iwao H, Kimura S, Fukui K, Nakamura A, Tamaki T, Ohkubo H, Nakanishi S, Abe Y (1990) Elevated angiotensinogen mRNA levels in rat liver by nephrectomy. Am J Physiol 2258:E413-E417

    Google Scholar 

  14. Soden M, Klett C, Hasmann T, Hackenthal E (1994) Angiotensinogen: an acute phase protein? Hypertension 23(suppl I):I-126–I-130

    CAS  Google Scholar 

  15. Lindpainter K, Lu W, Niedermajer N, Schieffer B, Just H, Ganten D, Drexler H (1993) Selective activation of cardiac angiotensinogen gene expression in post-infarction ventricular remodeling in the rat. J Mol Cell Cardiol 25:133–143

    Article  Google Scholar 

  16. Schunkert H, Ingelfinger JR, Hirsch AT, Tang SS, Litwin SE, Talsness CE, Dzau V (1992) Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure. J Clin Invest 90:1523–1529

    CAS  PubMed  Google Scholar 

  17. Oh BH, Ono S, Rockman HA, Ross J (1993) Myocardial hypertrophy in the ischemic zone induced by exercise in rats after coronary reperfusion. Circulation 87:598–607

    CAS  PubMed  Google Scholar 

  18. Ohkubo H, Kageyama R, Ujihara M, Hirose T, Inayama S, Nakanishi S (1983) Cloning and sequence analysis of cDNA for rat angiotensinogen. Proc Natl Acad Sci USA 80:2196–2200

    Article  CAS  PubMed  Google Scholar 

  19. Suzuki T, Kim HS, Kurabayashi M, Hamada H, Fujii H, Aikawa M, Watanabe M, Watanabe N, Sakomura Y, Yazaki Y, Nagai R (1996) Preferential differentiation of P19 mouse embryonal carcinoma cells into smooth muscle cells: use of retinoic acid and antisense against the central nervous system-specific POU transcription factor Brn-2. Circ Res 78:395–404

    CAS  PubMed  Google Scholar 

  20. Tso JY, Sun XH, Kao TH, Reece K, Wu R (1985) Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res 13:2485–2502

    Article  CAS  PubMed  Google Scholar 

  21. Ming M, Wu J, Lachance S, Delalandre A, Carriere S, Chan JS (1995) Beta-adrenergic receptors and angiotensinogen gene expression in mouse hepatoma cells in vitro. Hypertension 25:105–109

    CAS  PubMed  Google Scholar 

  22. Baker KM, Chernin MI, Wixson SK, Aceto JF (1990) Renin-angiotensin system involvement in pressure overload cardiac hypertrophy in rats. Am J Physiol 259:H324-H332

    CAS  PubMed  Google Scholar 

  23. Sadoshima J, Xu Y, Slayter HS, Izumo S (1993) Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984

    Article  CAS  PubMed  Google Scholar 

  24. Tamura K, Umemura S, Nyui N, Hibi K, Watanabe Y, Kobayashi I, Sumida Y, Ishigami T, Kihara M, Yabana M, Takagi N, Ishii M (1997) Regulation of cardiac angiotensinogen mRNA in vivo and in vitro. Heart Vessels Suppl 12:205–208

    Google Scholar 

  25. Klett C, Hellmann T, Suzuki F, Nakanishi S, Ohkubo H, Ganten D, Hackenthal E (1988) Induction of angiotensinogen mRNA in hepatocytes by angiotensin II and glucocorticoids. Clin Exp Hypertens 10:1009–1022

    CAS  Google Scholar 

  26. Klett C, Nobilling R, Gierschik P, Hackenthal E (1993) Angiotensin II stimulates the synthesis of angiotensinogen in hepatocytes by inhibiting adenylyl cyclase activity and stabilizing angiotensin mRNA. J Biol Chem 268:25095–25107

    CAS  PubMed  Google Scholar 

  27. Tamura K, Umemura S, Nyui N, Yamakawa T, Yamaguchi S, Ishigami T, Tanaka S, Tanimoto K, Takagi N, Sekihara H, Murakami K, Ishii M (1996) Tissuespecific regulation of angiotensinogen gene expression in spontaneously hypertensive rats. Hypertension 27:1216–1223

    CAS  PubMed  Google Scholar 

  28. Campbell DJ, Habener JF (1986) Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest 78:31–39

    CAS  PubMed  Google Scholar 

  29. Milsted A, Nishimura M, Brosnihan KB, Ferrario CM (1996) Differential regulation of angiotensinogen transcripts after renin infusion. Hypertension 28:678–681

    CAS  PubMed  Google Scholar 

  30. Hirsch AT, Talsnes CE, Schunkert H, Paul M, Dzau VJ, (1991) Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 69:475–482

    CAS  PubMed  Google Scholar 

  31. Johnston CI, Fabris B, Yoshida K (1993) The cardiac renin angiotensin system in heart failure. Am Heart J 126:756–760

    Article  CAS  PubMed  Google Scholar 

  32. Sun Y, Cleutjens JPM, Diaz-Arias AA, Weber KT (1994) Cardiac angiotensin converting enzyme and myocardial fibrosis in the rat. Cardiovasc Res 28:1423–1432

    Article  CAS  PubMed  Google Scholar 

  33. Meggs LG, Coupet J, Huang H, Cheng W, Li P, Capasso JM, Homcy CJ, Anversa P (1993) Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats. Circ Res 72:1149–1162

    CAS  PubMed  Google Scholar 

  34. Nio Y, Matsubara H, Murasawa S, Kanasaki M, Inada M (1995) Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J Clin Invest 95:46–54

    CAS  PubMed  Google Scholar 

  35. Gay RG (1990) Early and late effects of captopril treatment after large myocardial infarction in rats. J Am Coll Cardiol 16:967–977

    Article  CAS  PubMed  Google Scholar 

  36. Schoemaker RG, Debets JJM, Struyker-Boudier HAJ, Smits JFM (1991) Delayed but not immediate captopril therapy improves cardiac function in conscious rats following myocardial infarction. J Moll Cell Cardiol 23:187–197

    Article  CAS  Google Scholar 

  37. Swedberg K, Held P, Kjekshus J, Rasmussen K, Ryden L, Wedel H (1992) Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction: results of the Cooperative New Scandinavian Enalapril Study II (CONSENSUS II). N Engl J Med 327:678–684

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Heart Research Institute and Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-744, Seoul, Korea

    Hyo-Soo Kim, Byung-Hee Oh, Ki-Hoon Han, Se-Il Oh, Tae-Jin Youn, Cheol-Ho Kim, Myoung-Mook Lee, Young-Bae Park, Yun-Shik Choi & Young-Woo Lee

Authors
  1. Hyo-Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Byung-Hee Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ki-Hoon Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Se-Il Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tae-Jin Youn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cheol-Ho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Myoung-Mook Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Young-Bae Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yun-Shik Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Young-Woo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, HS., Oh, BH., Han, KH. et al. Reciprocal change in angiotensinogen mRNA expression in rat myocardium and liver after myocardial infarction. Heart Vessels 13, 1–8 (1998). https://doi.org/10.1007/BF02750637

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02750637

Key words

Search

Navigation