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

doi:10.1055/s-0031-1296310

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2010; 60(7): 445-451
DOI: 10.1055/s-0031-1296310

Antidiabetics

Editio Cantor Verlag Aulendorf (Germany)

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

Authors

Tetsuo Nishikawa

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan
Yoko Matsuzawa

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan
Sachiko Suematsu

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan
Jun Saito

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan
Masao Omura

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan
Tomoshige Kino

²Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

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 human primary 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.

Key words

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

Full Text

References

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