Skip to main content
SpringerLink
Log in

Oxidative stress-related proteins in a Conn’s adenoma tissue. Relevance for aldosterone’s prooxidative and proinflammatory activity

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background and aim: Angiotensin II (Ang II) induces oxidative stress (OxSt), which is essential for cardiovascular remodeling. Aldosterone also induces fibrosis and remodeling through direct effect on non-classical mineralocorticoid (MR) target tissues. However, studies on the role of aldosterone on OxSt and related factors in humans are lacking. Materials and methods: We assessed gene and protein expression of p22phox (RT-PCR and Western blot), NAD(P)H oxidase subunit essential for Superoxide production and gene expression of transforming growth fator (TGF) β, plasminogen activator inhibitor (PAI)-1, and heme oxygenase (HO)-1, effectors of OxSt (RT-PCR), in a Conn’s adenoma, removed from a patient with primary hyperaldosteronism. Ang II type 1 (AT1R) and MR receptors expression were also evaluated (RT-PCR). The normal adrenal tissue adjacent to the adenoma was used as control. Results: p22phox gene and protein expression were higher (31% and 53%, respectively) in the adrenal adenoma. TGFβ, PAI-1, and HO-1 gene expression were also higher (25%, 129%, and 25%, respectively) in the adrenal adenoma while AT1 R gene expression was similar (8%). The expression of MR in the adenoma was documented. Conclusions: This report demonstrates in a human model that the increased aldosterone production has effects on enzyme systems related to OxSt, enhancing the systemic fibrogenic effects of aldosterone excess through TGFβ and PAI-1 expression which was previously demonstrated only indirectly in vitro and in animal models. The presence of MR expression in the adenoma may link the hormone with the adenoma growth. Therefore, the results of this study derived from a single case might represent an important working hypothesis for further research in a larger number of cases to clarify the role of aldosterone overproduction on OxSt and its clinical relevance.

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. Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003, 91: 7A-11A.

    Article  Google Scholar 

  2. Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertension 2000, 18: 655–73.

    Article  CAS  Google Scholar 

  3. Dzau VJ. Tissue angiotensin and pathobiology of vascular disease. A unifying hypothesis. Hypertension 2001, 37: 1047–52.

    CAS  Google Scholar 

  4. Mehta PK, Griendling KK. Angiotensin II cell signaling. physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007, 92: C82–C97.

    Google Scholar 

  5. Fritsch Neves M, Schiffrin EL. Aldosterone: A risk factor for vascular disease. Curr Hypertens Rep 2003, 5: 59–65.

    Article  PubMed  Google Scholar 

  6. Gekle M, Mildenberger S, Freudinger R, Grossmann C. Altered collagen homeostasis in human aortic smooth muscle cells (HAoSMCs) induced by aldosterone. Pflugers Arch 2007, 454: 403–13.

    Article  CAS  PubMed  Google Scholar 

  7. Sun Y, Zhang J, Zhang JQ, Ramires FJ. Local angiotensin II and transforming growth factor beta 1 in renal fibrosis of rats. Hypertension 2000, 35: 1078–84.

    Article  CAS  PubMed  Google Scholar 

  8. Brown NJ, Vaughan DE, Fogo AB. Aldosterone and PAI-1: implications for renal injury. J Nephrol 2002, 15: 230–5.

    CAS  PubMed  Google Scholar 

  9. Farquharson CAJ, Struthers AD. Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 2000, 101: 594–7.

    Article  CAS  PubMed  Google Scholar 

  10. Virdis A, Neves MF, Amiri F, Viel E, Touyz RM, Schiffrin EL. Spironolactone improves angiotensin-induced vascular changes and oxidative stress in angiotensin II-infused rats. Hypertension 2002, 40: 504–10.

    Article  CAS  PubMed  Google Scholar 

  11. Epstain M. Aldosterone and the hypertensive kidney: its emerging role as a mediator of progressive renal disfunction: a paradigm shift. J Hypertension 2001, 19: 829–42.

    Article  Google Scholar 

  12. Rossi GP, Cavallin M, Nussdorfer GG, Pessina AC. The endothelin-aldosterone axis and cardiovascular diseases. J Cardiovasc Pharmacol 2001, 38(Suppl 2): S49–52.

    Article  CAS  PubMed  Google Scholar 

  13. Rajagopalan S, Duquaine D, King S, Pitt B, Patel P. Mineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation 2002, 105: 2212–6.

    Article  CAS  PubMed  Google Scholar 

  14. Pu Q, Neves MF Virdis A, Touyz RM, Schiffrin EL. Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling. Hypertension 2003, 42: 49–55.

    Article  CAS  PubMed  Google Scholar 

  15. Keidar S, Hayek T, Kaplan M, et al. Effect of eplerenone, a selective aldosterone blocker, on blood pressure, serum and macrophage oxidative stress, and atherosclerosis in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol 2003, 41: 955–63.

    Article  CAS  PubMed  Google Scholar 

  16. Calò LA, Zaghetto F, Pagnin E, et al. Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes. J Clin Endocrinol Metab 2004, 89: 1973–6.

    Article  PubMed  CAS  Google Scholar 

  17. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase. Role in cardiovascular biology and disease. Circ Res 2000, 86: 494–501.

    CAS  Google Scholar 

  18. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997, 37: 517–54.

    Article  CAS  PubMed  Google Scholar 

  19. Nath KA, Grande J, Croatt A, Haugen J, Kim Y, Rosenberg ME. Redox regulation of renal DNA synthesis, transforming growth factor-beta-1 and collagen gene expression. Kidney Int 1998, 53: 367–81.

    Article  CAS  PubMed  Google Scholar 

  20. Silacci P, Hayoz D. Oxidative stress as the triggering event for vascular remodelling. Nephrol Dial Transplant 1998, 13: 1343–6.

    Article  CAS  PubMed  Google Scholar 

  21. Calò LA, Pagnin E, Davis PA, Sartori M and Semplicini A. Oxidative stress-related factors in Bartter’s and Gitelman’s syndromes: relevance for angiotensin II signalling. Nephrol Dial Transplant 2003, 18: 1518–25.

    Article  PubMed  CAS  Google Scholar 

  22. Calò LA, Naso A, Carraro G et al. Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients. Nephrol Dial Transplant 2007, 22: 1413–9.

    Article  PubMed  Google Scholar 

  23. Azhar S, Cao L, Reaven E. Alteration of the adrenal antioxidant defense system during aging in rats. J Clin Invest 1995, 96: 1414–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Hornsby PJ. Steroid and xenobiotic effects on the adrenal cortex: mediation by oxidative and other mechanisms. Free Radic Biol Med 1989, 6: 103–15.

    Article  CAS  PubMed  Google Scholar 

  25. Eitzman DT, McCoy RD, Zheng X, et al. Bleomicin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene. J Clin Invest 1996, 97: 232–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Munger JS, Huang X, Kawakatsu H, et al. The integrin alpha v beta 6 binds and activates latent TG F beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999, 96: 319–28.

    Article  CAS  PubMed  Google Scholar 

  27. Ihn H. Pathogenesis of fibrosis: role of TGF-beta and CTGF. Curr Opin Rheumatol 2002, 14: 681–5.

    Article  CAS  PubMed  Google Scholar 

  28. Lijnen PJ, Petrov W, Fagard RH. Induction of cardiac fibrosis by transforming growth factor-β1. Mol Gen Metab 2000, 71: 418–35.

    Article  CAS  Google Scholar 

  29. Klahr S. Progression of chronic renal disease. Heart Dis 2001, 3: 205–9.

    Article  CAS  PubMed  Google Scholar 

  30. Diah S, Zhang GX, Nagai Y, et al. Aldosterone induces myofibroblastic transdifferentiation and collagen gene expression through the Rho-kinase dependent signaling pathway in rat mesangial cells. Exp Cell Res 2008, 314: 3654–62.

    Article  CAS  PubMed  Google Scholar 

  31. Takeda K, Ichiki T, Tokunou T, et al. Critical role of Rho-kinase and MEK-ERK pathways for angiotensin II-induced plasminogen activator inhibitor type-1 gene expression. Arterioscler Thromb Vasc Biol 2001, 21: 868–73.

    Article  CAS  PubMed  Google Scholar 

  32. Immenschuh S and Ramadori G. Gene regulation of heme oxygenase-1 as a therapeutic target. Biochem Pharmacol 2000, 60: 1121–8.

    Article  CAS  PubMed  Google Scholar 

  33. Rocha R, Rudolph AE, Frierdich GE, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002, 283: H1802–10.

    CAS  PubMed  Google Scholar 

  34. Rocha R, Martin-Berger CL, Yang P, Scherrer R, Delyani J, McMahon E. Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat heart. Endocrinology 2002, 143: 4828–36.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Via Giustiniani 2, 35128, Padova, Italy

    L. A. Calò MD, PhD, E. Pagnin, P. Mormino, G. P. Rossi & A. C. Pessina

  2. Department of Nutrition, University of California at Davis, Davis, California, USA

    P. A. Davis

  3. Department of Medical and Surgical Sciences, Endocrinology, University of Padua, Italy

    D. Armanini

Authors
  1. L. A. Calò MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Pagnin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. A. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Armanini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Mormino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. P. Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. C. Pessina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. A. Calò MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calò, L.A., Pagnin, E., Davis, P.A. et al. Oxidative stress-related proteins in a Conn’s adenoma tissue. Relevance for aldosterone’s prooxidative and proinflammatory activity. J Endocrinol Invest 33, 48–53 (2010). https://doi.org/10.1007/BF03346549

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03346549

Key-words

Search

Navigation