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Atorvastatin prevents end-organ injury in salt-sensitive hypertension: role of eNOS and oxidant stress
- Source :
- Hypertension (Dallas, Tex. : 1979). 44(2)
- Publication Year :
- 2004
-
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 (O 2 − ) 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 O 2 − 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 P 2 − (2632±316 versus 1176±112 counts/min per milligram in NS; P 2 α isoprostanes. Atorvastatin prevented the decrease in eNOS activity (1.5±0.3 nmol/min per gram protein) as well as the increase in O 2 − (1192±243 counts/min per milligram) and plasma 8-F 2 α 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.
- Subjects :
- Male
medicine.medical_specialty
Statin
Endothelium
Nitric Oxide Synthase Type III
medicine.drug_class
Atorvastatin
Heart Ventricles
Down-Regulation
Myocardial Reperfusion Injury
In Vitro Techniques
Left ventricular hypertrophy
Rats, Sprague-Dawley
Enos
Internal medicine
Internal Medicine
medicine
Animals
Pyrroles
Endothelial dysfunction
Aorta
biology
Chemistry
Sodium, Dietary
Organ Size
biology.organism_classification
medicine.disease
Angiotensin II
Rats
Nitric oxide synthase
Oxidative Stress
medicine.anatomical_structure
Endocrinology
Heptanoic Acids
Hypertension
biology.protein
Endothelium, Vascular
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide Synthase
medicine.drug
Subjects
Details
- ISSN :
- 15244563
- Volume :
- 44
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Accession number :
- edsair.doi.dedup.....613ff4b1c0c7363ab341c33b75bb86ed