Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats

Nora F. Banki, A. Vér, L. Wágner, A. Vannay, Peter Degrell, Agnes Prokai, Renata Gellai, Lilla Lenart, Dorottya Nagy Szakal, Eva Kenesei, Klara Rosta, G. Reusz, Attila J. Szabo, T. Tulassay, Chris Baylis, Andrea Fekete

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.

Original languageEnglish
Article numbere39938
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 28 2012

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diabetic nephropathy
Mineralocorticoid Receptor Antagonists
aldosterone
streptozotocin
Diabetic Nephropathies
Streptozocin
Adenosine Triphosphatases
Rats
sodium-potassium-exchanging ATPase
antagonists
Angiotensin-Converting Enzyme Inhibitors
Aldosterone
rats
angiotensin II
Angiotensin Receptor Antagonists
Kidney
Medical problems
kidneys
Glucose
diabetes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats. / Banki, Nora F.; Vér, A.; Wágner, L.; Vannay, A.; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya Nagy; Kenesei, Eva; Rosta, Klara; Reusz, G.; Szabo, Attila J.; Tulassay, T.; Baylis, Chris; Fekete, Andrea.

In: PLoS One, Vol. 7, No. 6, e39938, 28.06.2012.

Research output: Contribution to journalArticle

Banki, NF, Vér, A, Wágner, L, Vannay, A, Degrell, P, Prokai, A, Gellai, R, Lenart, L, Szakal, DN, Kenesei, E, Rosta, K, Reusz, G, Szabo, AJ, Tulassay, T, Baylis, C & Fekete, A 2012, 'Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats', PLoS One, vol. 7, no. 6, e39938. https://doi.org/10.1371/journal.pone.0039938
Banki, Nora F. ; Vér, A. ; Wágner, L. ; Vannay, A. ; Degrell, Peter ; Prokai, Agnes ; Gellai, Renata ; Lenart, Lilla ; Szakal, Dorottya Nagy ; Kenesei, Eva ; Rosta, Klara ; Reusz, G. ; Szabo, Attila J. ; Tulassay, T. ; Baylis, Chris ; Fekete, Andrea. / Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats. In: PLoS One. 2012 ; Vol. 7, No. 6.
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