Nitric oxide synthases (NOS) are a family of isoforms responsible for the synthesis of the potent dilator nitric oxide (NO). Expression of inducible NOS (iNOS) occurs in conditions of inflammation, and produces large amounts of NO. In pathological conditions iNOS is regarded as a harmful enzyme and is proposed to be a major contributor to diseases of the cardiovascular system such as atherosclerosis. In this review, we address the notion that iNOS is a detrimental enzyme in disease and discuss its potentially beneficial roles. Additionally, we describe other molecules associated with iNOS in diseases such as atherosclerosis, and current research on therapeutic inhibitors tested to reduced pathology associated with cardiovascular diseases (CVD).

• Klíčová slova
• COX-2, Cardiovascular diseases, Cyclooxygenase-2 (COX-2), Endothelial NOS (eNOS), Inducible NOS (iNOS), Nitric oxide synthase (NOS), Oxidative stress,
• MeSH
• kardiovaskulární nemoci metabolismus   MeSH
• lidé MeSH
• oxid dusnatý metabolismus   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• oxid dusnatý MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého MeSH

Research increasingly suggests that nitric oxide (NO) plays a role in the pathogenesis of schizophrenia. One important line of evidence comes from genetic studies, which have repeatedly detected an association between the neuronal isoform of nitric oxide synthase (nNOS or NOS1) and schizophrenia. However, the pathogenetic pathways linking nNOS, NO, and the disorder remain poorly understood. A deficit in sensorimotor gating is considered to importantly contribute to core schizophrenia symptoms such as psychotic disorganization and thought disturbance. We selected three candidate nNOS polymorphisms (Ex1f-VNTR, rs6490121 and rs41279104), associated with schizophrenia and cognition in previous studies, and tested their association with the efficiency of sensorimotor gating in healthy human adults. We found that risk variants of Ex1f-VNTR and rs6490121 (but not rs41279104) were associated with a weaker prepulse inhibition (PPI) of the acoustic startle reflex, a standard measure of sensorimotor gating. Furthermore, the effect of presence of risk variants in Ex1f-VNTR and rs6490121 was additive: PPI linearly decreased with increasing number of risk alleles, being highest in participants with no risk allele, while lowest in individuals who carry three risk alleles. Our findings indicate that NO is involved in the regulation of sensorimotor gating, and highlight one possible pathogenetic mechanism for NO playing a role in the development of schizophrenia psychosis.

• Klíčová slova
• Endophenotypes, NOS1, Nitric oxide, Prepulse inhibition, Schizophrenia, Startle,
• MeSH
• dospělí MeSH
• exony MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• minisatelitní repetice MeSH
• oxid dusnatý fyziologie   MeSH
• prepulsní inhibice genetika   MeSH
• schizofrenie genetika   MeSH
• senzorický gating genetika   MeSH
• synthasa oxidu dusnatého, typ I genetika   MeSH
• úleková reakce genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• NOS1 protein, human MeSH Prohlížeč
• oxid dusnatý MeSH
• synthasa oxidu dusnatého, typ I MeSH

The review briefly summarizes current knowledge of the bacterial nitric-oxide reductase (NOR). This membrane enzyme consists of two subunits, the smaller one contains haem C and the larger one two haems B and nonhaem iron. The protein sequence and structure of metal centres demonstrate the relationship of NOR to the family of terminal oxidases. The binuclear Fe-Fe reaction centre, consisting of antiferromagnetically coupled haem B and nonhaem iron, is analogous to Fe-Cu centre of terminal oxidases. The data on the structure and function of NOR and terminal oxidases suggest that all these enzymes are closely evolutionally related. The catalytic properties are determined most of all by the relatively high toxicity of nitric oxide as a substrate and the resulting strong need to maintain its concentration at nanomolar levels. A kinetic model of the action of the enzyme comprises substrate inhibition. NOR does not conserve the free energy of nitric oxide reduction because it does not work as a proton pump and, moreover, the protons coming into the reaction are taken from periplasm, i.e. they do not cross the membrane.

• MeSH
• Bacteria enzymologie   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidoreduktasy chemie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nitric-oxide reductase MeSH Prohlížeč
• oxid dusnatý MeSH
• oxidoreduktasy MeSH

Pulmonary hypertension is a condition characterized by vasoconstriction, vascular cell proliferation, inflammation, microthrombosis, and vessel wall remodelation. Pulmonary endothelial cells produce vasoactive substances with vasoconstrictive as well as vasodilatative effects. The imbalance of these endothelium-derived vasoactive substances induced by endothelial dysfunction is very important in the pathogenesis of PH. One of most important substances with vasodilatative effect is nitric oxide. We provide a comprehensive insight into role of NO in the pathgenesis of PH and discuss perspectives and challenges in PH therapy based on NO administration.

• Klíčová slova
• NO inhalation, Nitric oxide, Nitric oxide synthase, Pathophysiology, Pulmonary hypertension, Therapy,
• MeSH
• antihypertenziva farmakologie   terapeutické užití   MeSH
• lidé MeSH
• oxid dusnatý metabolismus   MeSH
• plicní hypertenze farmakoterapie   metabolismus   patofyziologie   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• vazodilatace fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antihypertenziva MeSH
• oxid dusnatý MeSH
• synthasa oxidu dusnatého, typ III MeSH

Leaf senescence is often associated with increased oxidative damage to cellular macromolecules by reactive oxygen species. However, very little is known about other radicals: gaseous free radical nitric oxide and related molecules--reactive nitrogen species. This review brings a short survey of the questions.

• MeSH
• dioxygenasy metabolismus   MeSH
• oxid dusnatý chemie   toxicita   MeSH
• reaktivní formy dusíku chemie   MeSH
• rostliny chemie   enzymologie   toxicita   MeSH
• vývoj rostlin MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• dioxygenasy MeSH
• oxid dusnatý MeSH
• reaktivní formy dusíku MeSH

Nitric oxide (NO) emerged as a key signal molecule in plants. During the last two decades impressive progress has been made in plant NO research. This small, redox-active molecule is now known to play an important role in plant immunity, stress responses, environmental interactions, plant growth and development. To more accurately and robustly establish the full spectrum of NO bioactivity in plants, it will be essential to apply methodological best practice. In addition, there are some instances of conflicting nomenclature within the field, which would benefit from standardization. In this context, we attempt to provide some helpful guidance for best practice associated with NO research and also suggestions for the cognate terminology.

• Klíčová slova
• S-nitrosylation, fluorescence, mitochondria, nitrate reductase, nitric oxide, nitric oxide synthase,
• MeSH
• oxid dusnatý * MeSH
• rostliny * MeSH
• vývoj rostlin MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• oxid dusnatý * MeSH

As a part of our extensive structure-activity relationship study of anti-inflammatory heterocycles, a novel series of 67 polysubstituted 2-aminopyrimidines was prepared bearing one (at the C-4 position of the pyrimidine ring) or two (in the C-4 and C-6 positions) (hetero)aryl substituents attached directly through the C-C bond. The key synthetic steps involved either Suzuki-Miyaura or Stille cross-coupling reactions carried out on easily available 4,6-dichloropyrimidines. All prepared compounds, except one, were able to inhibit immune-activated production of nitric oxide (NO) significantly. Moreover, several compounds were found to be low micromolar dual inhibitors of NO and prostaglandin E2 (PGE2) production. Although the exact mode of action of the prepared compounds remains to be elucidated, non-toxic dual inhibitors of NO and PGE2 production may have great therapeutic benefit in treatment of various inflammation diseases and deserve further preclinical evaluation.

• Klíčová slova
• Anti-inflammatory properties, Dual inhibitors, Nitric oxide, Prostaglandin E(2), Pyrimidine derivatives,
• MeSH
• dinoproston antagonisté a inhibitory   MeSH
• molekulární struktura MeSH
• myši inbrední C57BL MeSH
• oxid dusnatý antagonisté a inhibitory   MeSH
• pyrimidiny chemická syntéza   farmakologie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dinoproston MeSH
• oxid dusnatý MeSH
• pyrimidiny MeSH

Until now, the role of nitric oxide (NO) in cornea irradiated with UVB rays remains unknown. Therefore, we investigated nitric oxide synthase isomers (NOS), enzymes that generate NO, nitrotyrosine (NT), a cytotoxic byproduct of NO, and malondialdehyde (MDA), a byproduct of lipid peroxidation, in rabbit corneas repeatedly irradiated with UVB rays (312 nm, 1x daily for 6 days, the dose per day 1.01 J/cm2) using immunohistochemical methods. The biochemical measurement of nitrite and nitrate has been used for the indirect investigation of NO concentration in the aqueous humor. Results show that in contrast to normal corneas, where of the NOS isomers only endothelial nitric oxide synthase (NOS3) was expressed in a significant amount (in the epithelium and endothelium), in irradiated corneas all NOS isomers (also brain nitric oxide synthase, NOS1, and inducible nitric oxide synthase, NOS2) as well as an indirect measure of ONOO-formation and MDA were gradually expressed, first in the epithelium, the endothelium and the keratocytes beneath the epithelium and finally in the cells of all corneal layers and the inflammatory cells that invaded the corneal stroma. This was accompanied by an elevated concentration of NO in the aqueous humor. In conclusion, repeated irradiation with UVB rays evoked the stimulation of NO production, peroxynitrite formation (demonstrated by NT residues) and lipid peroxidation (evaluated by MDA staining).

• MeSH
• imunohistochemie MeSH
• komorová voda metabolismus   MeSH
• králíci MeSH
• kyselina peroxydusitá biosyntéza   MeSH
• malondialdehyd metabolismus   MeSH
• oxid dusnatý biosyntéza   MeSH
• peroxidace lipidů účinky záření   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• reaktivní formy dusíku biosyntéza   MeSH
• rohovka metabolismus   účinky záření   MeSH
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého, typ III MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-nitrotyrosine MeSH Prohlížeč
• kyselina peroxydusitá MeSH
• malondialdehyd MeSH
• oxid dusnatý MeSH
• proteiny nervové tkáně MeSH
• reaktivní formy dusíku MeSH
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého, typ III MeSH
• synthasa oxidu dusnatého MeSH
• tyrosin MeSH

We report here the in vitro measurements of nitric oxide in the cardiovascular system using a porphyrinic sensor specific for NO. Nitric oxide concentrations were measured directly in different parts of the heart and also in different arteries and veins, ranging from 100 microm to 5 mm in diameter. Highest NO. concentrations were found in the heart and particularly in the areas of aortic and pulmonary valves. The NO. concentration in the arteries was higher than in the veins. A clearcut positive correlation was obtained by plotting the vessel diameter and production of nitric oxide.

• MeSH
• calcimycin farmakologie   MeSH
• donory oxidu dusnatého farmakologie   MeSH
• ionofory farmakologie   MeSH
• kardiovaskulární systém metabolismus   MeSH
• králíci MeSH
• oxid dusnatý metabolismus   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• calcimycin MeSH
• donory oxidu dusnatého MeSH
• ionofory MeSH
• oxid dusnatý MeSH

Nitric-oxide synthase (NOS) catalyzes both coupled and uncoupled reactions that generate nitric oxide and reactive oxygen species. Oxygen is often the overlooked substrate, and the oxygen metabolism catalyzed by NOS has been poorly defined. In this paper we focus on the oxygen stoichiometry and effects of substrate/cofactor binding on the endothelial NOS isoform (eNOS). In the presence of both L-arginine and tetrahydrobiopterin, eNOS is highly coupled (>90%), and the measured stoichiometry of O(2)/NADPH is very close to the theoretical value. We report for the first time that the presence of L-arginine stimulates oxygen uptake by eNOS. The fact that nonhydrolyzable L-arginine analogs are not stimulatory indicates that the occurrence of the coupled reaction, rather than the accelerated uncoupled reaction, is responsible for the L-arginine-dependent stimulation. The presence of 5,6,7,8-tetrahydrobiopterin quenched the uncoupled reactions and resulted in much less reactive oxygen species formation, whereas the presence of redox-incompetent 7,8-dihydrobiopterin demonstrates little quenching effect. These results reveal different mechanisms for oxygen metabolism for eNOS as opposed to nNOS and, perhaps, partially explain their functional differences.

• MeSH
• arginin chemie   metabolismus   MeSH
• biopteriny analogy a deriváty   chemie   metabolismus   MeSH
• katalýza MeSH
• kyslík chemie   metabolismus   MeSH
• lidé MeSH
• nitrosaminy chemie   metabolismus   MeSH
• oxid dusnatý chemie   metabolismus   MeSH
• reaktivní formy kyslíku chemie   metabolismus   MeSH
• rekombinantní proteiny chemie   metabolismus   MeSH
• synthasa oxidu dusnatého, typ I chemie   metabolismus   MeSH
• synthasa oxidu dusnatého, typ III chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• arginin MeSH
• biopteriny MeSH
• kyslík MeSH
• N-nitrosoallyl-2,3-dihydroxypropylamine MeSH Prohlížeč
• nitrosaminy MeSH
• NOS3 protein, human MeSH Prohlížeč
• oxid dusnatý MeSH
• reaktivní formy kyslíku MeSH
• rekombinantní proteiny MeSH
• sapropterin MeSH Prohlížeč
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého, typ III MeSH