Skip to main content

Advertisement

SpringerLink
Log in

Aldosterone improves contractile function of adult rat ventricular cardiomyocytes in a non-acute way: potential relationship to the calcium paradox of aldosteronism

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Heart failure is accompanied by electrolyte disturbance including reduced calcium and sodium in the extracellular milieu but increased calcium within cells, a phenomenon called “calcium paradox”. Aldosteronism is considered as part of this disorder. Aldosterone antagonism is known to reduce cardiac mortality on top of standard therapies such as antagonism of the renin–angiotensin-system. However, the effect of aldosterone on cardiac function under basal conditions and conditions more closely related to those seen in heart failure remains elusive. In order to address this question the function of isolated cardiomyocytes was determined as unloaded cell shortening. Cardiomyocytes were isolated from adult rat hearts and cultured for 24 h in the presence of aldosterone. Thereafter, cell shortening was determined in cells that were electrically paced (0.5–2.0 Hz). The effect of aldosterone on cell shortening was investigated under basal and maximal inotropic stimulation, preincubation with angiotensin II and myocytes from spontaneously hypertensive rats. The composition of the culture medium was modified according to the extracellular milieu found in patients with end-stage heart failure. Aldosterone increased cell shortening in a frequency-dependent way under basal conditions and conditions of low calcium. It potentiated the effect of β-adrenoceptor stimulation, increased the formation of oxygen radicals, and increased diastolic and systolic calcium. In conclusion, chronic exposure to aldosterone improves the function of cardiomyocytes under basal conditions and electrolyte disturbances that mimic the situation found in heart failure patients.

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
Fig. 8

Similar content being viewed by others

References

  1. Alsafwah S, Laguardia SP, Nelson MD, Battin DL, Newman KP, Carbone LD, Weber KT (2008) Hypovitaminosis D in African Americans residing in Memphis, Tennessee with and without heart failure. Am J Med Sci 335:292–297

    Article  PubMed  Google Scholar 

  2. Arakelyan KP, Sahakyan YA, Hayrapetyan LR, Khudaverdyan DN, Ingelman-Sundberg M, Mkrtchian S, Ter-Markosyan AS (2007) Calcium-regulating peptide hormones and blood electrolyte balance in chronic heart failure. Regul Pept 142:95–100

    Article  CAS  PubMed  Google Scholar 

  3. Benitah J-P, Vassort G (1999) Aldosterone upregulates Ca2+ current in adult rat cardiomyocytes. Circ Res 85:1139–1145

    CAS  PubMed  Google Scholar 

  4. Boixel C, Gavillet B, Rougier J-S, Abriel H (2006) Aldosterone increases voltage-gated sodium current in ventricular myocytes. Am J Physiol Heart Circ Physiol 290:H2257–H2266

    Article  CAS  PubMed  Google Scholar 

  5. Chai W, Garrelds IM, Arulmani U, Schoemaker RG, Lamers JMJ, Danser AHJ (2005) Genomic and nongenomic effects of aldosterone in the rat heart: why is spironolactone cardioprotective? Br J Pharmacol 145:664–671

    Article  CAS  PubMed  Google Scholar 

  6. Chhokar VA, Sun Y, Bhattacharya SK, Ahokas RA, Myers LK, Xing Z, Smith RA, Gerling IC, Weber KT (2005) Hyperparathyroidism and the calcium paradox of aldosteronism. Circulation 111:871–878

    Article  CAS  PubMed  Google Scholar 

  7. Chun T-Y, Bloem LJ, Pratt JH (2003) Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes. Endocrinology 144:1712–1717

    Article  CAS  PubMed  Google Scholar 

  8. Fischer P, Hilfiker-Kleiner D (2007) Survival pathways in hypertrophy and heart failure: the gp130-STAT3 axis. Basic Res Cardiol 102:393–411

    Article  CAS  PubMed  Google Scholar 

  9. Hayashi H, Kobara M, Abe M, Tanaka N, Gouda E, Toba H, Yamada H, Tatsumi T, Nakata T, Matsubara H (2008) Aldosterone nongenomically produces NADPH oxidase-dependent reactive oxygen species and induces myocyte apoptosis. Hypertens Res 31:363–375

    Article  CAS  PubMed  Google Scholar 

  10. Jansen J, Gres P, Umschlag C, Heinzel FR, Degenhardt H, Schlüter K-D, Heusch G, Schulz R (2003) Parathyroid hormone-related peptide improves contractile function of stunned myocardium in rats and pigs. Am J Physiol Heart Circ Physiol 284:H49–H55

    CAS  PubMed  Google Scholar 

  11. Kiyomoto H, Rafiq K, Mostofa M, Nishiyama A (2008) Possible underlying mechanisms responsible for aldosterone, mineralocorticoid receptor-dependent renal injury. J Pharmacol Sci 108:399–405

    Article  CAS  PubMed  Google Scholar 

  12. Ladilov Y, Efe Ö, Schäfer C, Rother B, Kasseckert S, Abdallah Y, Meuter K, Schlüter K-D, Piper HM (2003) Reoxygenation-induced rigor-type contracture. J Mol Cell Cardiol 35:1481–1490

    Article  CAS  PubMed  Google Scholar 

  13. Langer M, Lüttecke D, Schlüter K-D (2003) Mechanism of the positive contractile effect of nitric oxide on rat ventricular cardiomyocytes with positive force/frequency relationship. Pflügers Arch 447:289–297

    Article  CAS  PubMed  Google Scholar 

  14. Lee AH, Mull RL, Keenan GF, Callegari PE, Dalinka MK, Einsen HJ, Mancini DM, DiSesa VJ, Attie MF (1994) Osteoporosis and bone morbidity in cardiac transplant recipients. Am J Med 96:35–41

    Article  CAS  PubMed  Google Scholar 

  15. Maack C, O’Rourke B (2007) Excitation–contraction coupling and mitochondrial energetics. Basic Res Cardiol 102:369–392

    Article  CAS  PubMed  Google Scholar 

  16. Mano A, Tatsumi T, Shiraishi J, Keira N, Nomura T, Takeda M, Nishikawa S, Yamanaka S, Matoba S, Kobara M, Tanaka H, Shirayama T, Takamatsu T, Nozawa Y, Matsubara H (2004) Aldosterone directly induces myocyte apoptosis through calcineurin-dependent pathways. Circulation 110:317–323

    Article  CAS  PubMed  Google Scholar 

  17. McCarron DA, Yung NN, Ugoretz BA, Krutzik S (1981) Disturbances of calcium metabolism in the spontaneously hypertensive rats. Hypertension 3(Suppl 1):I-162–I-167

    CAS  Google Scholar 

  18. Mihailidou AS, Mardini M, Funder JW (2004) Rapid, nongenomic effects of aldosterone in the heart mediated by ε protein kinase C. Endocrinology 145:773–780

    Article  CAS  PubMed  Google Scholar 

  19. Mihailidou AS, Funder JW (2005) Nongenomic effects of mineralcorticoid receptor activation in the cardiovascular system. Steroids 70:347–351

    Article  CAS  PubMed  Google Scholar 

  20. Mufti S, Wenzel S, Euler G, Piper HM, Schlüter K-D (2008) Angiotensin II-dependent loss of cardiac function: mechanisms and pharmacological targets attenuating this effect. J Cell Physiol 217:242–249

    Article  CAS  PubMed  Google Scholar 

  21. Perrier R, Richard S, Sainte-Marie Y, Rossier BC, Jaisser F, Hummler E, Bénitah J-P (2005) A direct relationship between plasma aldosterone and cardiac L-type Ca2+ current in mice. J Physiol 569:153–162

    Article  CAS  PubMed  Google Scholar 

  22. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Eng J Med 341:709–717

    Article  CAS  Google Scholar 

  23. Rebsamen MC, Perrier E, Gerber-Wicht C, Benitah J-P, Lang U (2004) Direct and indirect effects of aldosterone on cyclooxygenase-2 and interleukin-6 expression in rat cardiac cells in cultures after myocardial infarction. Endocrinology 145:3135–3142

    Article  CAS  PubMed  Google Scholar 

  24. Rude MK, Duhaney T-AS, Kuster GM, Judge S, Heo J, Colucci WS, Siwik DA, Sam F (2005) Aldosterone stimulates matrix metalloproteinases and reactive oxygen species in adult rat ventricular cardiomyocytes. Hypertension 46:555–561

    Article  CAS  PubMed  Google Scholar 

  25. Schlüter K-D, Schreiber D (2005) Adult ventricular cardiomyocytes: isolation and culture. Methods Mol Biol 290:305–314

    PubMed  Google Scholar 

  26. Stefanelli T, Pacher R, Woloszczuk W, Glogar D, Kaindl F (1992) Parathyroid hormone and calcium behavior in advanced congestive heart failure. Z Kardiol 81:121–125

    Google Scholar 

  27. Sun Y, Ahokas RA, Bhattacharya SK, Gerling IC, Carbone LD, Weber KT (2006) Oxidative stress in aldosteronism. Cardiovasc Res 71:300–309

    Article  CAS  PubMed  Google Scholar 

  28. Tastan I, Schreckenberg R, Mufti S, Abdallah Y, Piper HM, Schlüter K-D (2009) Parathyroid hormone improves contractile performance of adult rat ventricular cardiomyocytes at low concentrations in anon-acute way. Cardiovasc Res 82:77–83

    Article  CAS  PubMed  Google Scholar 

  29. Thomas M, Vidal A, Bhattacharya SK, Ahokas RA, Sun Y, Gerling IC, Weber KT (2007) Zinc dyshomeostasis in rats with aldosteronism. Response to spironolactone. Am J Physiol Heart Circ Physiol 2932:H2361–H2666

    Article  Google Scholar 

  30. Wenzel S, Soltanpour G, Schlüter K-D (2005) No correlation between the p38 MAPK pathway and the contractile dysfunction in diabetic cardiomyocytes. Pflugers Arch 451:328–337

    Article  CAS  PubMed  Google Scholar 

  31. Yamamuro M, Yoshimua M, Nakayama M, Abe K, Shono M, Suzuki S, Sakamoto T, Saito Y, Nakao K, Yasue H, Ogawa H (2006) Direct effects of aldosterone on cardiomyocytes in the presence of normal and elevated extracellular sodium. Endocrinology 147:1314–1321

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Deutsche Forschungsgemeinschaft (SFB 547, project A1) and a grant given by the Rhön GmbH.

Author information

Authors and Affiliations

  1. Physiologisches Institut, Justus-Liebig-University Giessen, Aulweg 129, 35392, Giessen, Germany

    Sibylle Wenzel, Ilhan Tastan, Yaser Abdallah, Rolf Schreckenberg & Klaus-Dieter Schlüter

Authors
  1. Sibylle Wenzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilhan Tastan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaser Abdallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rolf Schreckenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Klaus-Dieter Schlüter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Klaus-Dieter Schlüter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wenzel, S., Tastan, I., Abdallah, Y. et al. Aldosterone improves contractile function of adult rat ventricular cardiomyocytes in a non-acute way: potential relationship to the calcium paradox of aldosteronism. Basic Res Cardiol 105, 247–256 (2010). https://doi.org/10.1007/s00395-009-0059-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-009-0059-6

Keywords

Search

Navigation