Cellular and Molecular Mechanisms of Nitric Oxide–Induced Heart Muscle Relaxation

1998 ◽  
Vol 30 (4) ◽  
pp. 543-553 ◽  
Author(s):  
K.V Azatian ◽  
A.R White ◽  
R.J Walker ◽  
S.N Ayrapetyan
Keyword(s):  
Nitric Oxide ◽  
Heart Muscle ◽  
Molecular Mechanisms ◽  
Muscle Relaxation

scholarly journals Nitric Oxide and Oxidative Stress-Mediated Cardiovascular Functionality: From Molecular Mechanism to Cardiovascular Disease

2020 ◽  
Author(s):  
Weilue He ◽  
Maria Paula Kwesiga ◽  
Eyerusalem Gebreyesus ◽  
Sijia Liu
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiovascular System ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Contractile Function ◽  
Muscle Relaxation ◽  
Redox Balance ◽  
Heart Infarction ◽  
Artery Disease

The underlying pathology of most cardiovascular diseases (CVDs) such as coronary artery disease, high blood pressure, and stroke involves decreased cardiovascular contractility and anatomic alterations in cardiovascular structures. Nitric oxide (NO) regulates vascular tone and contractile function of myocardium and maintains blood vessel homeostasis. Interestingly, the effect of NO is like a double-edged sword in the body. Insufficient NO causes hypertension and atherosclerosis, while an overproduction of NO may foster inflammation and cause heart infarction and shock. In addition, growing evidences have shown that oxidative stress plays pivotal roles in the initiation and progression of CVDs. This chapter will discuss in detail the roles NO plays in the cardiovascular system under both physiological and pathological conditions. We will focus on: (1) the molecular mechanism of cardiovascular contraction, (2) NO/Ca2+-induced muscle relaxation, (3) NO-related structural change in blood vessels, and (4) redox balance in the cardiovascular system. The relationships between these molecular mechanisms and the characteristics of CVDs will be highlighted.

scholarly journals Hyperglycaemia-Induced Downregulation in Expression of nNOS Intramural Neurons of the Small Intestine in the Pig

2019 ◽  
Vol 20 (7) ◽  
pp. 1681 ◽  
Author(s):  
Michał Bulc ◽  
Katarzyna Palus ◽  
Michał Dąbrowski ◽  
Jarosław Całka
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Small Intestine ◽  
Enteric Nervous System ◽  
Molecular Mechanisms ◽  
Muscle Relaxation ◽  
Biologically Active ◽  
Enteric Neurons ◽  
Smooth Muscle Relaxation ◽  
Gi Tract

Diabetic autonomic peripheral neuropathy (PN) involves a broad spectrum of organs. One of them is the gastrointestinal (GI) tract. The molecular mechanisms underlying the pathogenesis of digestive complications are not yet fully understood. Digestion is controlled by the central nervous system (CNS) and the enteric nervous system (ENS) within the wall of the GI tract. Enteric neurons exert regulatory effects due to the many biologically active substances secreted and released by enteric nervous system (ENS) structures. These include nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS). It is a very important inhibitory factor, necessary for smooth muscle relaxation. Moreover, it was noted that nitrergic innervation can undergo adaptive changes during pathological processes. Additionally, nitrergic neurons function may be regulated through the synthesis of other active neuropeptides. Therefore, in the present study, using the immunofluorescence technique, we first examined the influence of hyperglycemia on the NOS- containing neurons in the porcine small intestine and secondly the co-localization of nNOS with vasoactive intestinal polypeptide (VIP), galanin (GAL) and substance P (SP) in all plexuses studied. Following chronic hyperglycaemia, we observed a reduction in the number of the NOS-positive neurons in all intestinal segments studied, as well as an increased in investigated substances in nNOS positive neurons. This observation confirmed that diabetic hyperglycaemia can cause changes in the neurochemical characteristics of enteric neurons, which can lead to numerous disturbances in gastrointestinal tract functions. Moreover, can be the basis of an elaboration of these peptides analogues utilized as therapeutic agents in the treatment of GI complications.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences

2019 ◽  
Vol 19 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Mahsa Hatami ◽  
Mina Abdolahi ◽  
Neda Soveyd ◽  
Mahmoud Djalali ◽  
Mansoureh Togha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
English Language ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Mitochondrial Dynamics ◽  
Nuclear Factor Κb ◽  
General Term ◽  
Neuroinflammatory Disease ◽  
Tnf Α ◽  
Factor Α

Objective: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer’s, Parkinson’s, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. Methods: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. Results: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. Conclusion: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

scholarly journals Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cell ◽  
Physical Exercise ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Stem Cell Biology ◽  
Myocardial Repair ◽  
Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

An Insight into the Role of Apoptosis and Autophagy in Nitric Oxide–Induced Articular Chondrocyte Cell Death

Cartilage ◽  
2020 ◽  
pp. 194760352097676
Author(s):  
Ekkapol Akaraphutiporn ◽  
Takafumi Sunaga ◽  
Eugene C. Bwalya ◽  
Wang Yanlin ◽  
Mwale Carol ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Chondrocyte Apoptosis ◽  
Protective Mechanism ◽  
Autophagic Flux ◽  
Qpcr Analysis

Objective To investigate the role and characterize the molecular mechanisms regulating apoptosis and autophagy in nitric oxide (NO)–induced chondrocyte cell death. Design Cell apoptosis and autophagy were evaluated in chondrocytes treated with sodium nitroprusside (SNP) combined with the presence or absence of interleukin-1 beta (IL-1β) and nutrient-deprived conditions. The concentration of nitrite was determined by Griess reaction. Activation of apoptosis and autophagy were determined by immunocytochemistry, Western blot, and quantitative real-time polymerase chain reaction (qPCR) analysis. Flow cytometry and MTT assay were used to assess cell viability. Results Cotreatment of chondrocytes with SNP and IL-1β under nutrient-deprived condition potentially enhanced the effect of NO-induced cell death. Immunocytochemistry, Western blot, and qPCR analysis indicated that treatment of chondrocytes with SNP significantly reduced autophagic activity, autophagic flux, and multiple autophagy-related (Atg) genes expression. These findings were associated with an increase in ERK, Akt, and mTOR phosphorylation, whereas autophagy induction through mTOR/p70S6K inhibition by rapamycin significantly suppressed NO-induced cell apoptosis. Furthermore, the cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 activation in response to apoptosis was weakly detected. These results corresponded with a significant increase in apoptosis-inducing factor (AIF) expression, suggesting the involvement of the caspase-independent pathway. Conclusions These results demonstrate that in chondrocyte cultures with cells induced into an osteoarthritis state, NO inhibits autophagy and induces chondrocyte apoptosis mainly, but not completely through the caspase-independent pathway. Our data suggest that autophagy is a protective mechanism in the pathogenesis of osteoarthritis and could be proposed as a therapeutic target for degenerative joint diseases.

Transdermal Nitroglycerine in the Management of Pain Associated with Primary Dysmenorrhoea: A Multinational Pilot Study

1997 ◽  
Vol 25 (1) ◽  
pp. 41-44 ◽  
Author(s):  
O Ré ◽  
Keyword(s):  
Nitric Oxide ◽  
Pain Relief ◽  
Muscle Relaxation ◽  
Nitric Oxide Donor ◽  
Controlled Study ◽  
Smooth Muscle Relaxation ◽  
Uterine Contractility ◽  
Double Blind ◽  
Patch Application ◽  
Endogenous Nitric Oxide

Endogenous nitric oxide mediates smooth-muscle relaxation with subsequent vasodilatation in the vascular, pulmonary, gastrointestinal and genitourinary tissues. Transdermal nitroglycerine (a nitric oxide donor) has been found effective in inhibiting uterine contractility during premature labour. Sixty-five women with histories of moderate-to-severe pain associated with menses were treated with nitroglycerine patches that delivered 0.2 or 0.1 mg/h. Patches were applied as necessary during the first 3 days of the menstrual cycle for up to three consecutive cycles. Pain intensity was assessed at baseline and at 30 min and at 1, 2 and 4 h after patch application. Most patients obtained pain relief with the first dose of the first day. Pain relief was satisfactory to excellent in 90% of the patients. Headache was reported by 20% of the patients, most often in patients using two consecutive patches. A randomized, double-blind, placebo-controlled study is underway in an attempt to confirm the above findings.

Acid and neutral sphingomyelinases: roles and mechanisms of regulation

2004 ◽  
Vol 82 (1) ◽  
pp. 27-44 ◽  
Author(s):  
Norma Marchesini ◽  
Yusuf A Hannun
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Caveolin 1 ◽  
Niemann Pick Disease ◽  
Extracellular Stimuli ◽  
Niemann Pick ◽  
Hydrolysis Of ◽  
Pick Disease

Ceramide, an emerging bioactive lipid and second messenger, is mainly generated by hydrolysis of sphingomyelin through the action of sphingomyelinases. At least two sphingomyelinases, neutral and acid sphingo myelinases, are activated in response to many extracellular stimuli. Despite extensive studies, the precise cellular function of each of these sphingomyelinases in sphingomyelin turnover and in the regulation of ceramide-mediated responses is not well understood. Therefore, it is essential to elucidate the factors and mechanisms that control the activation of acid and neutral sphingomyelinases to understand their the roles in cell regulation. This review will focus on the molecular mechanisms that regulate these enzymes in vivo and in vitro, especially the roles of oxidants (glu ta thi one, peroxide, nitric oxide), proteins (saposin, caveolin 1, caspases), and lipids (diacylglycerol, arachidonic acid, and ceramide).Key words: sphingomyelinase, ceramide, apoptosis, Niemann-Pick disease, FAN (factor associated with N-SMase activation).

scholarly journals Glyoxalase I is a novel nitric-oxide-responsive protein

1999 ◽  
Vol 344 (3) ◽  
pp. 837-844 ◽  
Author(s):  
Atsushi MITSUMOTO ◽  
Kwi-Ryeon KIM ◽  
Genichiro OSHIMA ◽  
Manabu KUNIMOTO ◽  
Katsuya OKAWA ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Culture Medium ◽  
Molecular Mechanisms ◽  
Peptide Mapping ◽  
Glyoxalase I ◽  
Dependent Manner ◽  
Human Endothelial Cells ◽  
Native Form ◽  
No Donors ◽  
Dose Dependent

To clarify the molecular mechanisms of nitric oxide (NO) signalling, we examined the NO-responsive proteins in cultured human endothelial cells by two-dimensional (2D) PAGE. Levels of two proteins [NO-responsive proteins (NORPs)] with different pI values responded to NO donors. One NORP (pI 5.2) appeared in response to NO, whereas another (pI 5.0) disappeared. These proteins were identified as a native form and a modified form of human glyoxalase I (Glox I; EC 4.4.1.5) by peptide mapping, microsequencing and correlation between the activity and the isoelectric shift. Glox I lost activity in response to NO, and all NO donors tested inhibited its activity in a dose-dependent manner. Activity and normal electrophoretic mobility were restored by dithiothreitol and by the removal of sources of NO from the culture medium. Glox I was selectively inactivated by NO; compounds that induce oxidative stress (H2O2, paraquat and arsenite) failed to inhibit this enzyme. Our results suggest that NO oxidatively modifies Glox I and reversibly inhibits the enzyme's activity. The inactivation of Glox I by NO was more effective than that of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), another NO-sensitive enzyme. Thus Glox I seems to be a novel NO-responsive protein that is more sensitive to NO than G3PDH.

Sign in / Sign up

Export Citation Format

Share Document