Atorvastatin causes depressor and sympatho-inhibitory effects with upregulation of nitric oxide synthases in stroke-prone spontaneously hypertensive rats

Takuya Kishi, Yoshitaka Hirooka, Yasushi Mukai, Hiroaki Shimokawa, Akira Takeshita

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Objective: Recent studies have suggested that statins decrease blood pressure in hypertensive animals and upregulate endothelial nitric oxide synthase (eNOS) expression. However, the effects of statins on the expression of nitric oxide synthase (NOS) in the brain and the sympathetic nervous system remain to be elucidated. The aim of this study was thus to examine the effects of atorvastatin on blood pressure, sympathetic nerve activity, and the expression of NOS in stroke-prone spontaneously hypertensive rats (SHRSP) as well as in Wistar-Kyoto (WKY) rats. Methods: The animals received atorvastatin (50 mg/kg per day) for 30 days. Systolic blood pressure and heart rate were evaluated using the tail-cuff method. Urinary norepinephrine excretion was measured for 24 h. The expression of eNOS, neuronal NOS (nNOS), and inducible NOS (iNOS) in the brain (cortex, cerebellum, hypothalamus and brainstem), aorta and heart were determined by Western blot analysis. Results: Systolic blood pressure and 24-h urinary norepinephrine excretion were significantly decreased in SHRSP, but not in WKY, after the treatment with atorvastatin. The eNOS and iNOS expression in the brain and aorta was significantly increased in atorvastatin-treated SHRSP and WKY. However, the nNOS expression in the brain was not altered in the atorvastatin-treated group. Conclusions: These results suggest that atorvastatin decreases blood pressure, at least in part via the reduction of sympathetic nervous system activity in SHRSP. They also suggest that this sympatho-inhibitory effect may be mediated by an increase in NO production, with the upregulation of eNOS expression in the brain.

Original languageEnglish
Pages (from-to)379-386
Number of pages8
JournalJournal of hypertension
Volume21
Issue number2
DOIs
Publication statusPublished - 2003 Feb 1

Keywords

  • Blood pressure
  • Brain
  • Hypertension
  • Nitric oxide synthase
  • Statins
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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