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Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions
Open accessAbstract
Objectives We tested the hypothesis that pravastatin (PRA) activates endothelial nitric oxide synthase (eNOS).Background Pravastatin has been found to have clinical benefits beyond those predicted by its actions in reducing plasma low density lipoprotein cholesterol (LDL). Both PRA and simvastatin (SIM) are equally effective in reducing LDL, but only PRA reduces platelet aggregation and is an effective vasodilator. Nitric oxide (NO) also inhibits platelet aggregation and vasodilates.Methods We determined PRA and SIM effects on vasorelaxation in aortic rings and NO production by cultured bovine aortic endothelial cells. Nitric oxide was measured by using a NO electrode and by an assay for conversion of hemoglobin to methemoglobin. Specificity of NOS activation was tested by using the NOS inhibitor nitro-L-arginine methyl ester (L-NAME, 1 mmol/liter) in the presence or absence of excess L-arginine (L-ARG, 1 mmol/liter).Results Endothelium-dependent vasorelaxation was maximal with acetylocholine (ACH, 100%), followed by PRA (62.8%) and then SIM (37.1%). Direct measurement of NO confirmed that vasorelaxation is due to NO release and showed that PRA and ACH had similar dose-dependent effects on NO production, while SIM was only 25% to 30% as effective. Methemoglobin assay confirmed these results and demonstrated their specificity for NOS activity. The L-NAME blunted the responses to 45% of initial values. Excess L-ARG reversed this effect and potentiated NO production to 133% of initial levels.Conclusions Both PRA and SIM activate eNOS, but SIM is much less effective. Clinical benefits with PRA not explained by LDL reductions may be the result of an independent action of PRA on eNOS activation.
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“Pravastatin has been demonstrated to enhance nitric oxide generation by augmenting the activity of endothelial nitric oxide synthase (eNOS) [25].”
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Metadata
- Authors
- Kaesemeyer, W. H., Caldwell, R. B., Huang, J., & Caldwell, R. W.
- Affiliations
- Augusta University (US)
- Corresponding author
- Kaesemeyer, Wayne H.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 33
- Issue
- 1
- Pages
- 234-241
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2169537677
- Cited by
- 343
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 7 · 2014: 8 · 2013: 10 · 2012: 9
- FWCI
- 19.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- pravastatin, simvastatin, endothelial nitric oxide synthase, nitric oxide, endothelium-dependent relaxation, platelet aggregation, vasodilation, L-NAME, L-arginine, statins, LDL cholesterol lowering, aortic endothelial cells
- MeSH terms
- Animals, Anticholesteremic Agents, Cattle, Endothelium, Vascular, Enzyme Activation, Cholesterol, LDL, Male, Platelet Aggregation, Vasodilation, Pravastatin, Rats, Sprague-Dawley, Nitric Oxide Synthase, Culture Techniques, Rats, Nitric Oxide Synthase Type III
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