Pitavastatin upregulates nitric oxide synthases in the kidney of spontaneously hypertensive rats and wistar-kyoto rats

Gaizun Hu, Osamu Ito, Rong Rong, Akihiro Sakuyama, Takahiro Miura, Daisuke Ito, Yoshiko Ogawa, Masahiro Kohzuki

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND Clinical trials show potent renoprotective effects of pitavastatin (PTV), although the precise mechanism for these renoprotective effects is not fully clarified. The aim of this study was to examine the antihypertensive and renoprotective effects of PTV, focusing on the nitric oxide (NO) system. METHODS Male, 6-week-old, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were randomized to receive vehicle or PTV (2 mg/kg bodyweight) for 8 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks. After 8 weeks, plasma biochemical parameters and renal histology were examined. NO synthase isoform (neuronal, nNOS; inducible, iNOS; and endothelial, eNOS) expression and eNOS phosphorylation were examined by western blotting. RESULTS PTV attenuated hypertension and albuminuria development in SHR. PTV decreased glomerular desmin expression and medullary interstitial fibrosis in SHR. PTV tended to increase plasma NO in both strains but significantly increased urinary NO excretion only in WKY. PTV significantly increased nNOS and eNOS expression, enhanced eNOS phosphorylation at serine1177, and inhibited eNOS phosphorylation at threonine495 in the kidney of both strains. CONCLUSIONS PTV treatment led to increased renal NOS expression and upregulated eNOS activity in both SHR and WKY. The antihypertensive and renoprotective effects of PTV may be related to upregulation of the NO system.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalAmerican Journal of Hypertension
Volume31
Issue number10
DOIs
Publication statusPublished - 2018 Sep 11

Keywords

  • albuminuria
  • antihypertension
  • blood pressure
  • hydroxymethylglutaryl-CoA reductase inhibitors
  • hypertension
  • nitric oxide
  • nitric oxide synthase pitavastatin
  • phosphorylation
  • renoprotection

ASJC Scopus subject areas

  • Internal Medicine

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