Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets?

Rochette, Luc; Lorin, Julie; Zeller, Marianne; Guilland, Jean-Claude; Lorgis, Luc; Cottin, Yves; Vergely, Catherine

doi:10.1016/j.pharmthera.2013.07.004

Cited by 456Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionEicosanoids and Hypertension Pharmacology

Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets?

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Rochette, Luc, Lorin, Julie, Zeller, Marianne, Guilland, Jean-Claude, Lorgis, Luc, Cottin, Yves, Vergely, Catherine·2013·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2013.07.004

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Abstract

Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor availability. The importance of BH(4) as a critical regulator of eNOS function suggests that BH(4) may be a rational therapeutic target in vascular disease states. BH(4) oxidation appears to be a major contributor to vascular dysfunction associated with hypertension, ischemia/reperfusion injury, diabetes and other cardiovascular diseases as it leads to the increased formation of oxygen-derived radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in vascular NO production and transport result in endothelial dysfunction leading to various cardiovascular disorders. However, some disorders including a wide range of functions in the neuronal, immune and cardiovascular system were associated with the over-production of NO. Inhibition of the enzyme should be a useful approach to treat these pathologies. Therefore, it appears that both a lack and excess of NO production in diseases can have various important pathological implications. In this context, NOS modulators (exogenous and endogenous) and their therapeutic effects are discussed.

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Studies on pulmonary hypertension show improvement in the 6-min walking distance with BH4.
“Studies on pulmonary hypertension also show improvement in the 6-min walking distance (788).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [788]

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Authors: Rochette, L., Lorin, J., Zeller, M., Guilland, J.-C., Lorgis, L., Cottin, Y., & Vergely, C.
Affiliations: Université de Bourgogne (FR)
Inserm (FR)
Corresponding author: Rochette, Luc
ORCID: Rochette, Luc
Zeller, Marianne
Lorgis, Luc
Cottin, Yves
Vergely, Catherine
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2013-12
Volume: 140
Issue: 3
Pages: 239-257
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2013.07.004
OpenAlex: W2035714184
Cited by: 456
References: 201
Citations by year: 2026: 17 · 2025: 36 · 2024: 29 · 2023: 50 · 2022: 42 · 2021: 40 · 2020: 31 · 2019: 39 · 2018: 36 · 2017: 40 · 2016: 29 · 2015: 37 · 2014: 23 · 2013: 5
FWCI: 3.45
Type: journal article
Language: en
Open access: green
ube.hal.science
Licence: other-oa
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords: nitric oxide synthase inhibition, nitric oxide, oxidative stress, cardiovascular disease, asymmetric dimethylarginine, tetrahydrobiopterin, endothelial dysfunction, endothelial nitric oxide synthase, NOS isoforms, calmodulin, hypertension, ischemia-reperfusion injury, diabetes mellitus, vascular dysfunction, therapeutic target
MeSH terms: Animals, Cardiovascular Diseases, Enzyme Inhibitors, Humans, Nitric Oxide, Oxidative Stress, Nitric Oxide Synthase

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Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets?

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