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

Autor: Catherine Vergely, Marianne Zeller, Jean-Claude Guilland, Yves Cottin, Luc Lorgis, Julie Lorin, Luc Rochette
Přispěvatelé: Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques (U866, Lipides et nutrition, équipe 5) (LPPCM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Vergely, Catherine
Rok vydání: 2013
Předmět:
NO inhibitors
free radicals
030204 cardiovascular system & hematology
Protein degradation
Pharmacology
Nitric Oxide
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
BH 4
0302 clinical medicine
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
cardiovascular disease
Enos
medicine
Animals
Humans
Pharmacology (medical)
Enzyme Inhibitors
Endothelial dysfunction
Reactive nitrogen species
030304 developmental biology
NO synthases
0303 health sciences
biology
Tetrahydrobiopterin
biology.organism_classification
medicine.disease
[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
3. Good health
ADMA
Nitric oxide synthase
Oxidative Stress
chemistry
Biochemistry
Cardiovascular Diseases
biology.protein
Nitric Oxide Synthase
Asymmetric dimethylarginine
medicine.drug
Zdroj: Pharmacology and Therapeutics
Pharmacology and Therapeutics, Elsevier, 2013, 140 (3), pp.239-257. ⟨10.1016/j.pharmthera.2013.07.004⟩
Pharmacology and Therapeutics, 2013, 140 (3), pp.239-257. ⟨10.1016/j.pharmthera.2013.07.004⟩
ISSN: 0163-7258
Popis: International audience; 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 overproduction 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.
Databáze: OpenAIRE
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