Atorvastatin prevents end-organ injury in salt-sensitive hypertension: Role of eNOS and oxidant stress

Ming Sheng Zhou, Edgar A. Jaimes, Leopoldo Raij

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Statins, inhibitors of cholesterol biosynthesis, are endowed with pleiotropic effects that may contribute to their favorable clinical results. Hypertensive Dahl salt-sensitive (DS) rats have endothelial dysfunction and cardiorenal injury associated with decreased NO bioavailability and increased superoxide (O2-) production linked to a functional upregulation of angiotensin II. We investigated whether atorvastatin (30 mg/kg per day; by gavage) would prevent endothelial nitric oxide (eNOS) downregulation and the increase in O2- in DS rats, thereby reducing end-organ injury. DS rats given a high-salt diet (4% NaCl) for 10 weeks developed hypertension (systolic blood pressure [SBP] 200±8 versus 150±2 mm Hg in DS rats fed 0.5% NaCl diet [NS]; P<0.05), impaired endothelium-dependent relaxation, functional upregulation of endothelin-1, left ventricular hypertrophy (LVH; 30%), and proteinuria (167%), accompanied by downregulation of aortic eNOS activity (0.7±0.2 versus 1.8±0.3 nmol/min per gram protein in NS; P<0.05) and increased aortic O 2-(2632±316 versus 1176±112 counts/min per milligram in NS; P<0.05) and plasma 8-F2α isoprostanes. Atorvastatin prevented the decrease in eNOS activity (1.5±0.3 nmol/min per gram protein) as well as the increase in O2 -(1192±243 counts/min per milligram) and plasma 8-F 2α isoprostanes, reduced LVH and proteinuria, and normalized endothelial function and vascular response to endothelin-1, although reduction in SBP was modest (174±8 mm Hg). Atorvastatin combined with removal of high salt normalized aortic eNOS activity, SBP, LVH, and proteinuria. These findings strongly suggest that concomitant prevention of vascular eNOS downregulation and inhibition of oxidative stress may contribute to the protection against end-organ injury afforded by this statin in salt-sensitive hypertension.

Original languageEnglish (US)
Pages (from-to)186-190
Number of pages5
JournalHypertension
Volume44
Issue number2
DOIs
StatePublished - Aug 1 2004

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Keywords

  • Hypertension
  • Nitric oxide synthase
  • Oxidative stress
  • Sodium dependent
  • Statins

ASJC Scopus subject areas

  • Internal Medicine

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