TY - JOUR
T1 - Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets?
AU - Rochette,Luc,
AU - Lorin,Julie,
AU - Zeller,Marianne,
AU - Guilland,Jean-Claude,
AU - Lorgis,Luc,
AU - Cottin,Yves,
AU - Vergely,Catherine,
Y1 - 2013/07/13/
PY - 2013/06/13/received
PY - 2013/06/14/accepted
PY - 2013/7/18/entrez
PY - 2013/7/19/pubmed
PY - 2014/5/20/medline
KW - 6-pyruvoyl tetrahydropterin synthase
KW - 7,8-dihydroneopterin 30 triphosphate
KW - 8-Oxoguanine DNA glycosylase
KW - ADMA
KW - AF
KW - AGXT2
KW - AP-1
KW - ARE
KW - AT
KW - ApoE-KO
KW - AscH(−)
KW - BH(3)
KW - BH(4)
KW - CAAs
KW - CAT
KW - CATs
KW - CR
KW - CV
KW - CaM
KW - Cardiovascular disease
KW - DDAHs
KW - DHFR
KW - DHPR
KW - DM
KW - DMA
KW - DMGV
KW - DNTP
KW - ERK
KW - FAD
KW - FMN
KW - FOS
KW - FOXO
KW - Finkel–Biskis–Jinkins osteosarcoma
KW - Free radicals
KW - GP
KW - GPx
KW - GSH
KW - GTP
KW - GTP cyclohydrolase 1
KW - GTP-CH
KW - HIF
KW - HSP
KW - JNK
KW - LDL
KW - LTL
KW - MAO
KW - MAPK
KW - MDA
KW - MT
KW - N(G)-monomethyl-l-arginine
KW - N-nitro-l-arginine
KW - N-omega-hydroxy-l-arginine
KW - NADPH
KW - NADPH oxidase
KW - NF-κB
KW - NO
KW - NO inhibitors
KW - NO synthases
KW - NOHA
KW - NOX
KW - NTPH
KW - Nrf2
KW - OGG1
KW - OS
KW - PAH
KW - PCD
KW - PRMT
KW - PTPS
KW - Prx
KW - RNS
KW - ROS
KW - Ref-1
KW - S-adenosyl-l-homocysteine
KW - S-adenosyl-l-methionine
KW - SAH
KW - SAM
KW - SDMA
KW - SOD
KW - SR
KW - TH
KW - TocH
KW - Trx
KW - UA
KW - activator protein 1
KW - alanine-glyoxylate aminotransferase 2
KW - angiotensin
KW - antioxidant response element
KW - apolipoprotein E knockout
KW - ascorbate anion
KW - asymmetric dimethylarginine
KW - atrial fibrillation
KW - c-Jun N-terminal kinase
KW - calmodulin
KW - carbonyl reductase
KW - cardiovascular
KW - catalases
KW - cationic amino acid transporters
KW - cationic amino acids
KW - diabetes mellitus
KW - dihydrofolate reductase
KW - dihydropteridine reductase
KW - dimethylamines
KW - dimethylarginine dimethylaminohydrolases
KW - eGFR
KW - estimated glomerular filtration rate
KW - extracellular signal-regulated kinase
KW - flavin adenine dinucleotide
KW - flavin mononucleotide
KW - forkhead protein
KW - glutathione
KW - glutathione peroxidases
KW - glutathioneperoxidase
KW - guanosine triphosphate
KW - heat shock protein
KW - hypoxia-inducible factor
KW - l-Arg
KW - l-NMMA
KW - l-NNA
KW - l-arginine
KW - leukocyte telomere length
KW - low-density lipoprotein
KW - malondialdehyde
KW - metallothionein
KW - mitogen-activated protein kinase
KW - monoamine oxidase
KW - neuronal tryptophan hydroxylase
KW - nicotinamide dinucleotide phosphate
KW - nitric oxide
KW - nuclear factor erythroid 2-related factor 2
KW - nuclear factor κB
KW - oxidative stress
KW - peroxyredoxin
KW - phenylalanine hydroxylase
KW - protein arginine methyl transferase
KW - pterin-4a-carbinolamine dehydratase
KW - reactive nitrogen species
KW - reactive oxygen species
KW - redox factor-1
KW - sepiapterin reductase
KW - siRNAs
KW - small interfering ribonucleic acids
KW - superoxide dismutase
KW - symmetric dimethylarginine
KW - tHcy
KW - tetrahydrobiopterin
KW - thioredoxin
KW - tocopherol
KW - total plasma homocysteine
KW - trihydrobiopterin radical
KW - tyrosine hydroxylase
KW - uric acid
KW - y+L AA
KW - y+LAT transporters
KW - α-keto-δ-(N(G),N(G)-dimethylguanidino)valeric acid
SP - 239
EP - 57
JF - Pharmacology & therapeutics
JO - Pharmacol Ther
VL - 140
IS - 3
N2 - 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.
SN - 1879-016X
UR - https://www.unboundmedicine.com/medline/citation/23859953/Nitric_oxide_synthase_inhibition_and_oxidative_stress_in_cardiovascular_diseases:_possible_therapeutic_targets
DB - PRIME
DP - Unbound Medicine
ER -
