title: Protective effects of mineralocorticoid receptor blockade against neuropathy in experimental diabetic rats.
abstract: OBJECTIVE
  Mineralocorticoid receptor (MR) blockade is an effective treatment for hypertension and diabetic nephropathy. There are no data on the effects of MR blockade on diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether MRs are present in the peripheral nerves and to investigate the effectiveness of MR blockade on DPN in streptozotocin (STZ)-induced diabetic rats.
  
  
  METHODS
  Expression of MR protein and messenger RNA (mRNA) was examined in the peripheral nerves using Western blot analysis and RT-PCR. We next studied the effects of the selective MR antagonist eplerenone and the angiotensin II receptor blocker candesartan on motor and sensory nerve conduction velocity (NCV), morphometric changes and cyclooxygenase-2 (COX-2) gene and NF-κB protein expression in the peripheral nerves of STZ-induced diabetic rats.
  
  
  RESULTS
  Expression of MR protein and mRNA in peripheral nerves was equal to that in the kidney. Motor NCV was significantly improved by 8 weeks of treatment with either eplerenone (39.1 ± 1.2 m/s) or candesartan (46.4 ± 6.8 m/s) compared with control diabetic rats (33.7 ± 2.0 m/s) (p < 0.05). Sensory NCV was also improved by treatment with candesartan or eplerenone in diabetic rats. Eplerenone and candesartan caused significant improvement in mean myelin fibre area and mean myelin area compared with control diabetic rats (p < 0.05). COX-2 mRNA and NF-κB protein were significantly elevated in the peripheral nerves of diabetic rats compared with control rats, and treatment with eplerenone or candesartan reduced these changes in gene expression (p < 0.05).
  
  
  CONCLUSIONS
  MR blockade may have neuroprotective effects on DPN.
authors.affiliation: Division of Endocrinology and Hypertension, Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takata
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: A
authors.initials: A
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: T
authors.initials: T
authors.lastname: Yoneda
authors.forename: M
authors.initials: M
authors.lastname: Demura
authors.forename: K
authors.initials: K
authors.lastname: Yagi
authors.forename: S
authors.initials: S
authors.lastname: Karashima
authors.forename: M
authors.initials: M
authors.lastname: Yamagishi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000077545:Eplerenone; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D000451:Mineralocorticoid Receptor Antagonists; D016328:NF-kappa B; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D013777:Tetrazoles; D013148:Spironolactone; D000077545:Eplerenone; C081643:candesartan