Effect of atorvastatin on aldosterone production induced by glucose, LDL or angiotensin II in human renal mesangial cells

Tetsuo Nishikawa, Yoko Matsuzawa, Sachiko Suematsu, Jun Saito, Masao Omura, Tomoshige Kino

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Nephropathy is a major complication of diabetes mellitus, thus development of rational therapeutic means is critical for improving public health. It was previously reported that human mesangial cells locally produced aldosterone, a steroid hormone that plays an important role in the development of diabetic nephropathy. The present experiments clarified the effect of glucose, LDL and angiotensin II, the molecules frequently elevated in patients with diabetic nephropathy, on aldosterone production in humanprimary mesangial cells. These cells expressed the CYP11B2 mRNA, a rate-limiting enzyme in the aldosterone biosynthesis. LDL and angiotensin II stimulated CYP11B2 mRNA expression in these cells, while a high concentration of glucose, angiotensin II and/or LDL increased aldosterone production. Importantly, atorvastatin (CAS 134523-03-8), an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor, strongly suppressed their effects on aldosterone production. Atorvastatin also suppressed positive effects of these compounds on the mRNA expression of the angiotensin II receptor type 1, thus atorvastatin exerted its negative effect in part through changing expression of this receptor. Since elevated levels of glucose and LDL, and increased action of the renin-angiotensin-aldosterone system is known to participate in the progression of diabetic nephropathy, it is speculated that the mesangial endocrine system that produces aldosterone locally is a promising therapeutic target for diabetic nephropathy where HMG-CoA reductase inhibitors provide a beneficial effect.

Original languageEnglish
Pages (from-to)445-451
Number of pages7
JournalArzneimittel-Forschung/Drug Research
Volume60
Issue number7
Publication statusPublished - 2010
Externally publishedYes

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Keywords

  • Aldosterone
  • Angiotensin II type 1 receptor
  • Atorvastatin
  • CAS 134523-03-8
  • CYP11B2
  • Mesangial cells

ASJC Scopus subject areas

  • Drug Discovery
  • Medicine(all)

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