Cited by 343Nitric Oxide and Endothelin EffectsLipoproteins and Cardiovascular HealthCardiovascular Health and Disease Prevention

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Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions

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Kaesemeyer, Wayne H., Caldwell, Ruth B., Huang, Jianzhong, Caldwell, R.William·1999·Journal of the American College of Cardiology

DOI 10.1016/s0735-1097(98)00514-2

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Abstract

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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Background
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Method
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Background
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Background
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Background
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BackgroundInfluential
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“[250] W.”
Background
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“The CRP-lowering effect of statins may be mediated by NO, since statins are known to promote its production [99,100].”
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“It has been demonstrated that 427 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 19 dietary nitrate acts as a precursor to NO in a dose-dependent mannerwhereby a single 428 serving…”
BackgroundInfluential
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“It is, however, well known that HMG-CoA reductase inhibitors affect the expression and activity of eNOS, increasing bioavailability of NO (Laufs et al., 1997, 1998; John et al., 1998; Kaesemeyer et al., 1999).”
Background
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Background
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Background
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“(20) demonstrating some eNOS agonist properties of pravastatin.”
Background
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Role of Cardiac ATP-Sensitive K+ Channels Induced by HMG CoA Reductase Inhibitor in Ischemic Rabbit Hearts.
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“Different studies suggested that the effect of statins on BP may be due to the regulation of vascular tone through an increase in nitric oxide (31), a decrease in plasma aldosterone level (32), a decrease in endothelin-1 production (33), a reduction in vascular angiotensin II type-1 receptors (34), or an increase in a…”
Background

Authors: Kaesemeyer, W. H., Caldwell, R. B., Huang, J., & Caldwell, R. W.
Affiliations: Augusta University (US)
Corresponding author: Kaesemeyer, Wayne H.
ORCID: Kaesemeyer, Wayne H.
Caldwell, Ruth B.
Huang, Jianzhong
Caldwell, R.William
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)
DOI: 10.1016/s0735-1097(98)00514-2
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5310 d)
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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Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions

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