Role Of Nitric Oxide In Regulation Research Articles

Allelopathic effect of pyrogallic acid on cyanobacterium Microcystis aeruginosa: The regulatory role of nitric oxide and its significance for controlling harmful algal blooms (HABs)

Utilization of allelochemicals to inhibit overgrowth of toxic cyanobacteria is considered to be an environmentally friendly approach. However, the regulatory role of the signaling molecule nitric oxide (NO) on cyanobacteria under allelopathic stress remains unanswered. Here we demonstrate that the effect of NO on the cyanobacterium Microcystis aeruginosa depends on allelopathic stress of pyrogallic acid (PA). The experimental results revealed that general stimulation of M. aeruginosa by PA occurred within the concentration range 0.4–0.8 mg/L. In parallel with increasing concentration of PA (1.6–16.0 mg/L), the growth of M. aeruginosa was observed to decrease. The effect of NO on M. aeruginosa was evaluated by addition of the NO scavenger hemoglobin. In the stimulation stage, intracellular NO was seen to decreased to modulate the level of reactive oxygen species (ROS) and to maintain redox homeostasis of the cells. In the inhibition stage, the physiological characteristics of M. aeruginosa were changed significantly. Additionally, the accumulation of S-nitrosothiol by M. aeruginosa indicated that the high concentrations of PA induced nitric oxidative stress in M. aeruginosa. This study provides a new thought to understand the role of NO in controlling harmful algal blooms through the allelopathic effect of aquatic macrophytes.

The Multiple Faces of Nitric Oxide in Chronic Granulomatous Disease: A Comprehensive Update.

Nitric oxide (NO), a signaling molecule, regulates multiple biological functions, including a variety of physiological and pathological processes. In this regard, NO participates in cutaneous inflammations, modulation of mitochondrial functions, vascular diseases, COVID-19, neurologic diseases, and obesity. It also mediates changes in the skeletal muscle function. Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by the malfunction of phagocytes caused by mutations in some of the genes encoding subunits of the superoxide-generating phagocyte NADPH (NOX). The literature consulted shows that there is a relationship between the production of NO and the NADPH oxidase system, which regulates the persistence of NO in the medium. Nevertheless, the underlying mechanisms of the effects of NO on CGD remain unknown. In this paper, we briefly review the regulatory role of NO in CGD and its potential underlying mechanisms.

The regulatory role of nitric oxide in morphine-induced analgesia in the descending path of pain from the dorsal hippocampus to the dorsolateral periaqueductal gray.

Nitric oxide (NO) levels in brain nuclei, such as the hippocampus and brainstem, are involved in morphine analgesia, but the relationship between the dorsal hippocampus (dH) and the dorsolateral periaqueductal gray matter (dlPAG) needs to be clarified, which is our goal. Wistar rats were simultaneously equipped with a stereotaxic device with unilateral guide cannula at dH and dlPAG. After recovery, they were divided into control and experimental groups. Formalin (50μl of 2.5%) was inoculated into the left hind paw of the rat. Morphine (6mg/kg) was administered intraperitoneally (i.p.) 10min before formalin injection. L-Arginine (0.25, 0.5, 1 and 2μg/rat), and L-NAME (0.25, 0.5, 1 and 2μg/rat), unrelatedly or with respect in the order of injection were used in the nuclei before morphine injection (i.p.). Activation of the neuronal NO synthase (nNOS) in the brains of all animals was measured using NADPH-diaphorase, a selective biochemical marker of nNOS. Morphine reduced inflammatory pain in the early and late stages of the rat formalin test. The morphine response was attenuated before injection of single L-arginine but not L-NAME in the two target areas. However, the acute phase result was stopped due to L-NAME pretreatment. When L-NAME was injected into dlPAG before injecting L-arginine at dH, the morphine response did not decrease at all, indicating a modulatory role of NO in dlPAG, which was confirmed by NADPH-d staining. High levels of NO in dlPAG may regulate the pain process in downward synaptic interactions. Nitric oxide is involved in the dH and dlPAG in morphine-induced analgesia in the rat formalin test. Morphine has analgesic effects in both phases of the rat formalin test. The morphine response is reduced in two stages by injection of the NO precursor L-arginine but not the nNOS inhibitor L-NAME in the dH and dlPAG. By injecting L-NAME before L-arginine in both nuclei, the morphine-induced response returns in the early stages. Due to the initial injection of L-NAME into dlPAG and the subsequent injection of L-arginine at dH, morphine analgesia is not reduced at all, indicating NO modulation in the pain pathway from dH to dlPAG.

Regulatory Role of Nitric Oxide in Cutaneous Inflammation.

Nitric oxide (NO), a signaling molecule, regulates biological functions in multiple organs/tissues, including the epidermis, where it impacts permeability barrier homeostasis, wound healing, and antimicrobial defense. In addition, NO participates in cutaneous inflammation, where it exhibits pro-inflammatory properties via the cyclooxygenase/prostaglandin pathway, migration of inflammatory cells, and cytokine production. Yet, NO can also inhibit cutaneous inflammation through inhibition of T cell proliferation and leukocyte migration/infiltration, enhancement of T cell apoptosis, as well as through down-regulation of cytokine production. Topical applications of NO-releasing products can alleviate atopic dermatitis in humans and in murine disease models. The underlying mechanisms of these discrepant effects of NO on cutaneous inflammation remain unknown. In this review, we briefly review the regulatory role of NO in cutaneous inflammation and its potential, underlying mechanisms.

Nitric oxide releasing nanomatrix gel treatment inhibits venous intimal hyperplasia and improves vascular remodeling in a rodent arteriovenous fistula

Vascular access is the lifeline for hemodialysis patients and the single most important component of the hemodialysis procedure. Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis patients, but nearly 60% of AVFs created fail to successfully mature due to early intimal hyperplasia development and poor outward remodeling. There are currently no therapies available to prevent AVF maturation failure. First, we showed the important regulatory role of nitric oxide (NO) on AVF development by demonstrating that intimal hyperplasia development was reduced in an overexpressed endothelial nitric oxide synthase (NOS3) mouse AVF model. This supported the rationale for the potential application of NO to the AVF. Thus, we developed a self-assembled NO releasing nanomatrix gel and applied it perivascularly at the arteriovenous anastomosis immediately following rat AVF creation to investigate its therapeutic effect on AVF development. We demonstrated that the NO releasing nanomatrix gel inhibited intimal hyperplasia formation (more than 70% reduction), as well as improved vascular outward remodeling (increased vein diameter) and hemodynamic adaptation (lower wall shear stress approaching the preoperative level and less vorticity). Therefore, direct application of the NO releasing nanomatrix gel to the AVF anastomosis immediately following AVF creation may enhance AVF development, thereby providing long-term and durable vascular access for hemodialysis.

Role of nitric oxide in orthodontic tooth movement (Review).

Nitric oxide (NO) is an ubiquitous signaling molecule that mediates numerous cellular processes associated with cardiovascular, nervous and immune systems. NO also plays an essential role in bone homeostasis regulation. The present review article summarized the effects of NO on bone metabolism during orthodontic tooth movement in order to provide insight into the regulatory role of NO in orthodontic tooth movement. Orthodontic tooth movement is a process in which the periodontal tissue and alveolar bone are reconstructed due to the effect of orthodontic forces. Accumulating evidence has indicated that NO and its downstream signaling molecule, cyclic guanosine monophosphate (cGMP), mediate the mechanical signals during orthodontic-related bone remodeling, and exert complex effects on osteogenesis and osteoclastogenesis. NO has a regulatory effect on the cellular activities and functional states of osteoclasts, osteocytes and periodontal ligament fibroblasts involved in orthodontic tooth movement. Variations of NO synthase (NOS) expression levels and NO production in periodontal tissues or gingival crevicular fluid (GCF) have been found on the tension and compression sides during tooth movement in both orthodontic animal models and patients. Furthermore, NO precursor and NOS inhibitor administration increased and reduced the tooth movement in animal models, respectively. Further research is required in order to further elucidate the underlying mechanisms and the clinical application prospect of NO in orthodontic tooth movement.

209 Inducible nitric oxide synthase regulates epidermal permeability barrier homeostasis

Though a regulatory role for nitric oxide (NO) in diverse cutaneous functions is well known, whether NO impacts permeability homeostasis remains unexplored. Here, we utilized inducible nitric oxide synthase (iNOS) KO mice to explore the role of NO and iNOS in epidermal homeostasis. Although iNOS KO and wild type mice looked grossly similar, iNOS KO mice displayed a significant abnormality in permeability barrier recovery in comparison with wild type mice, and epidermal biophysical properties were comparable between these two groups at baseline. Consistent with delayed barrier recovery, the expression of genes strongly linked to permeability barrier homeostasis, including epidermal lipid synthetic enzymes (HMGCoA reductase, fatty acid synthase, serine palmitoyltransferase), and keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) was significantly decreased in iNOS KO mice. Pertinently, topical applications of NO upregulated the expression of epidermal mRNA for lipid production and keratinocyte differentiation in parallel with accelerated barrier recovery in iNOS KO mice. Taken together, these results indicate that the generation of NO by epidermal iNOS is crucial for epidermal homeostasis.

Nitric Oxide Negatively Regulates Larval Metamorphosis in Hard-Shelled Mussel (Mytilus coruscus)

Marine invertebrates undergo distinct life cycles and development processes, and some undergo a metamorphic transition from pelagic larvae to benthic juvenile. Previous studies have shown that the second messenger nitric oxide (NO) plays important roles in regulating larval metamorphosis in marine invertebrates. However, this regulatory function is not conserved. Herein, we investigated the regulatory role of NO in larval metamorphosis in Hard-shelled mussel (Mytilus coruscus). Pharmacological experiments revealed that after exposure to nitric oxide synthase (NOS) inhibitors, the larval metamorphosis rate was increased significantly. By contrast, exposure to NO donors significantly reduced the larval metamorphosis rate. To further investigate the function of NO in metamorphosis, we cloned the NOS cDNA sequence from M. coruscus (McNOS), analyzed amino acid sequences of McNOS from different species, and measured McNOS mRNA temporal expression alongside the molecular chaperone heat shock protein 90 (HSP90) in different larval stages. The results showed that NOS proteins share a highly conserved domain sequence in different species, even in invertebrates and vertebrates, but their classification among invertebrates and vertebrates is not the same. Except for the umbo veliger stage, McNOS mRNA was expressed at low levels in pediveliger larval and post-larvae stage, indicating a potential inhibitory function for NO in larval metamorphosis. Meanwhile, HSP90 mRNA expression was correspondingly high in the umbo veliger stage and lower in the pediveliger larval and post-larvae stage, indicating potential functional synergism. Interestingly, McNOS enzyme activity in different larval stages was inconsistent with its mRNA expression. Metamorphosis assays of pharmacological treatments combined with McNOS and HSP90 gene expression and NOS enzyme activity analyses indicated that NO acts as a suppressor to regulate metamorphosis in M. coruscus, regardless of whether nitric oxide is endogenous or exogenous.

Downregulation of Nitric Oxide Collaborated with Radiotherapy to Promote Anti-Tumor Immune Response via Inducing CD8+ T Cell Infiltration.

The production of nitric oxide (NO) is a key feature of immunosuppressive myeloid cells, which impair T cell activation and proliferation via reversibly blocking interleukin-2 receptor signaling. NO is mainly produced from L-arginine by inducible NO synthase (iNOS). Moreover, L-arginine is an essential element for T cell proliferation and behaviors. Impaired T cell function further inhibits anti-tumor immunity and promotes tumor progression. Previous studies indicated that radiotherapy activated anti-tumor immune responses in multiple tumors. However, myeloid-derived cells in the tumor microenvironment may neutralize these responses. We hypothesized that iNOS, as an important regulator of the immunosuppressive effects in myeloid-derived cells, mediated radiation resistance of cancer cells. In this study, we used 1400W dihydrochloride, a potent small-molecule inhibitor of iNOS, to explore the regulatory roles of NO in anti-tumor immunity. Radiotherapy and iNOS inhibition by 1400W collaboratively suppressed tumor growth and increased survival time, as well as increased tumor-infiltrating CD8+ T cells and specific inflammatory cytokine levels, in both lung and breast cancer cells in vivo. Our results also suggested that myeloid cell-mediated inhibition of T cell proliferation was effectively counteracted by radiation and 1400W-mediated NO blockade in vitro. Thus, these results demonstrated that iNOS was an important regulator of radiotherapy-induced antitumor immune responses. The combination of radiotherapy with iNOS blockade might be an effective therapy to improve the response of tumors to clinical radiation.

Nitric oxide and phytoglobin PHYTOGB1 are regulatory elements in the Solanum lycopersicum-Rhizophagus irregularis mycorrhizal symbiosis.

The regulatory role of nitric oxide (NO) and phytoglobins in plant response to pathogenic and mutualistic microbes has been evidenced. However, little is known about their function in the arbuscular mycorrhizal (AM) symbiosis. We investigated whether NO and phytoglobin PHYTOGB1 are regulatory components in the AM symbiosis. Rhizophagus irregularis in vitro-grown cultures and tomato plants were used to monitor AM-associated NO-related root responses as compared to responses triggered by the pathogen Fusarium oxysporum. A genetic approach was conducted to understand the role of PHYTOGB1 on NO signaling during both interactions. After a common early peak in NO levels in response to both fungi, a specific NO accumulation pattern was triggered in tomato roots during the onset of the AM interaction. PHYTOGB1 was upregulated by the AM interaction. By contrast, the pathogen triggered a continuous NO accumulation and a strong downregulation of PHYTOGB1. Manipulation of PHYTOGB1 levels in overexpressing and silenced roots led to a deregulation of NO levels and altered mycorrhization and pathogen infection. We demonstrate that the onset of the AM symbiosis is associated with a specific NO-related signature in the host root. We propose that NO regulation by PHYTOGB1 is a regulatory component of the AM symbiosis.

Nitric oxide in plant-fungal interactions.

Whilst many interactions with fungi are detrimental for plants, others are beneficial and result in improved growth and stress tolerance. Thus, plants have evolved sophisticated mechanisms to restrict pathogenic interactions while promoting mutualistic relationships. Numerous studies have demonstrated the importance of nitric oxide (NO) in the regulation of plant defence against fungal pathogens. NO triggers a reprograming of defence-related gene expression, the production of secondary metabolites with antimicrobial properties, and the hypersensitive response. More recent studies have shown a regulatory role of NO during the establishment of plant-fungal mutualistic associations from the early stages of the interaction. Indeed, NO has been recently shown to be produced by the plant after the recognition of root fungal symbionts, and to be required for the optimal control of mycorrhizal symbiosis. Although studies dealing with the function of NO in plant-fungal mutualistic associations are still scarce, experimental data indicate that different regulation patterns and functions for NO exist between plant interactions with pathogenic and mutualistic fungi. Here, we review recent progress in determining the functions of NO in plant-fungal interactions, and try to identify common and differential patterns related to pathogenic and mutualistic associations, and their impacts on plant health.

Nitric Oxide and the Neuroendocrine Control of the Osmotic Stress Response in Teleosts

The involvement of nitric oxide (NO) in the modulation of teleost osmoresponsive circuits is suggested by the facts that NO synthase enzymes are expressed in the neurosecretory systems and may be regulated by osmotic stimuli. The present paper is an overview on the research suggesting a role for NO in the central modulation of hormone release in the hypothalamo-neurohypophysial and the caudal neurosecretory systems of teleosts during the osmotic stress response. Active NOS enzymes are constitutively expressed by the magnocellular and parvocellular hypophysiotropic neurons and the caudal neurosecretory neurons of teleosts. Moreover, their expression may be regulated in response to the osmotic challenge. Available data suggests that the regulatory role of NO appeared early during vertebrate phylogeny and the neuroendocrine modulation by NO is conservative. Nonetheless, NO seems to have opposite effects in fish compared to mammals. Indeed, NO exerts excitatory effects on the electrical activity of the caudal neurosecretory neurons, influencing the amount of peptides released from the urophysis, while it inhibits hormone release from the magnocellular neurons in mammals.

Nitric oxide affects cadmium-induced changes in the lichen Ramalina farinacea

Metabolic responses of epiphytic lichen Ramalina farinacea to cadmium (Cd) and/or nitric oxide (NO) scavenger (cPTIO) were studied. Accumulation of Cd and other metallic nutrients was not affected by cPTIO while total and absorbed amounts differed. Cd-induced NO formation was suppressed by cPTIO but ROS signal was synergistically enhanced, confirming that NO is essential to keep ROS under control. This excessive ROS generation could be a reason for depleted amount of all fatty acids, including SFAs, MUFAs and PUFAs. Total content of fatty acids reached 3.89 mg/g DW in control with linoleic (40%), palmitic (24%), oleic (12.8%) and stearic (8%) acids as major compounds: interestingly, shift in relative ratio of saturated (from 40 to 35% of total FAs) versus polyunsaturated fatty acids (from 42 to 48% of total FAs) was observed. Glutathione was suppressed by all treatments but Krebs acids were almost unaffected by cPTIO, indicating no regulatory role of NO in their accumulation. On the contrary, Cd-induced elevation in NO signal was related to increase in ascorbate and proline content while cPTIO suppressed it, indicating a tight relation between NO and these metabolites. Data are compared also with algae and vascular plants to show similarities between various life lineages.

Nitric oxide mediates aluminum-induced citrate secretion through regulating the metabolism and transport of citrate in soybean roots

Citrate secretion is a kind of typical strategy for plant against aluminum (Al) toxicity. However, the signaling process in Al-activated citrate secretion needs to be clarified. Physiological and biochemical methods as well as gene expression analysis were employed to examine the regulatory roles of nitric oxide (NO) in Al-activated citrate secretion in soybean roots. Application of NO donor alleviated root growth inhibition and decreased Al content in Al-treated root apices. Al-induced NO production and citrate secretion were further elevated by NO donor, but inhibited by NO scavenger. Inhibition of citrate synthase (CS) or plasma membrane (PM) H+-ATPase activity significantly decreased Al-induced secretion of citrate, but inhibition of aconitase (ACO) activity enhanced citrate secretion under Al stress. Furthermore, NO mediated Al-stimulated CS and PM H+-ATPase activities, but decreased ACO activity under Al stress. Further investigation showed that NO modulated Al-activated transcriptional expression of CS and PM H+-ATPase as well as GmMATE. Overexpression of GmMATE in soybean hairy roots caused an enhanced Al-induced citrate efflux and Al resistance. Our findings suggest that NO-dependent up-regulation of citrate synthesis and activation of PM H+-ATPase-coupled MATE transporter co-transport system participates in Al-activated citrate exudation, thus conferring plant resistance to Al toxicity.

Elevated CO2-induced production of nitric oxide differentially modulates nitrate assimilation and root growth of wheat seedlings in a nitrate dose-dependent manner.

Wheat is a major staple food crop worldwide contributing approximately 20% of total protein consumed by mankind. The nitrogen and protein concentration of wheat crop and grain often decline as a result of exposure of the crop to elevated CO2 (EC). The changes in nitrogen (N) assimilation, root system architecture, and nitric oxide (NO)-mediated N signaling and expression of genes involved in N assimilation and high affinity nitrate uptake were examined in response to different nitrate levels and EC in wheat. Activity of enzyme nitrate reductase (NRA) was downregulated under EC both in leaf and root tissues. Plants grown under EC displayed enhanced production of NO and more so when nitrate supply was high. Based on exogenous supply of NO, inhibitors of NO production, and NO scavenger, regulatory role of NO on EC mediated changes in root morphology and NRA was revealed. The enhanced NO production under EC and high N levels negatively regulated the transcript abundance of NR and high affinity nitrate transporters (HATS).

Exploring the regulatory role of nitric oxide (NO) and the NO-p38MAPK/cGMP pathway in larval settlement of the bryozoan Bugula neritina

The bryozoan Bugula neritina is a cosmopolitan marine fouling species that causes major fouling problems in sub-tropical waters. Settlement of B. neritina larvae can be triggered without an obvious external cue. Here, the negative regulatory role of nitric oxide (NO) during larval settlement of B. neritina was demonstrated to be mediated by cyclic guanosine monophosphate (cGMP). Although the regulatory role of the NO-p38 MAPK signaling axis in larval settlement was not evident, inhibition of nitric oxide synthase (NOS) led to the deactivation of p38 MAPK. Exclusive localization of NO and NO signaling components in sensory-related organs of the larvae is consistent with its signal transduction function in metamorphosis. Overall, this study provides new insights into the regulatory roles of the NO-p38MAPK/cGMP pathway in B. neritina settlement.

Nitric Oxide in the Pathogenesis and Treatment of Tuberculosis.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is globally known as one of the most important human pathogens. Mtb is estimated to infect nearly one third of the world's population with many subjects having a latent infection. Thus, from an estimated 2 billion people infected with Mtb, less than 10% may develop symptomatic TB. This indicates that the host immune system may constrain pathogen replication in most infected individuals. On entering the lungs of the host, Mtb initially encounters resident alveolar macrophages which can engulf and subsequently eliminate intracellular microbes via a plethora of bactericidal mechanisms including the generation of free radicals such as reactive oxygen and nitrogen species. Nitric oxide (NO), a key anti-mycobacterial molecule, is detected in the exhaled breath of patients infected with Mtb. Recent knowledge regarding the regulatory role of NO in airway function and Mtb proliferation paves the way of exploiting the beneficial effects of this molecule for the treatment of airway diseases. Here, we discuss the importance of NO in the pathogenesis of TB, the diagnostic use of exhaled and urinary NO in Mtb infection and the potential of NO-based treatments.

АДАПТАЦИЯ НАСОСНОЙ ФУНКЦИИ СЕРДЦА К МЫШЕЧНОЙ ДЕЯТЕЛЬНОСТИ

Aim. The aim of this article is to study movement quickness, speed endurance, heart pumping function, mental efficiency, and the role of nitric oxide (NO) in the conditions of body adaptation to muscular trainings of various intensity. Materials and Methods. By means of human studies, we established the consistent pattern of heart pumping function, mental efficiency, and physiological properties of the locomotor system. In order to study some regulation mechanisms of heart pumping function we conducted rat studies to define the regulatory role of nitric oxide (NO). Results. We found out that with the improvement of athletic performance the indices of movement quickness and speed endurance increase. Their rate of change depends on the character and intensity of muscular loads performed. Moderate muscular load contributes to more intense development of the quantitative indices of mental efficiency. The training process aimed at the development of endurance creates conditions for more energy efficient functioning of the cardiovascular system of rats in comparison with animals adapted to movement quickness. Conclusion. Changes in the nitric oxide (NO) content of the tissues of rats trained for movement quickness and general endurance mostly coincide with previously established consistent patterns of variation in norepinephrine and acetylcholine concentration in the heart tissues of trained rats.

АДАПТАЦИЯ НАСОСНОЙ ФУНКЦИИ СЕРДЦА К МЫШЕЧНОЙ ДЕЯТЕЛЬНОСТИ

Абзалов Рустем Ринатович, кандидат биологических наук, доцент кафедры теории и методики физической культуры, спорта и лечебной физической культуры, Казанский (Приволжский) федеральный университет. 420008, Республика Татарстан, г. Казань, ул. Кремлевская, 18. E-mail: 2902207@mail.ru, ORCID: 0000-0003-4940-1502. Абзалов Наиль Ильясович, доктор биологических наук, доцент, заведующий кафедрой теории и методики физической культуры, спорта и лечебной физической культуры, Казанский (Приволжский) федеральный университет. 420008, Республика Татарстан, г. Казань, ул. Кремлевская, 18. E-mail: nailabzalov@mail.ru, ORCID: 0000-0002-8428-2724. Абзалов Ринат Абзалович, доктор биологических наук, профессор, профессор кафедры теории и методики физической культуры, спорта и лечебной физической культуры, Казанский (Приволжский) федеральный университет. 420008, Республика Татарстан, г. Казань, ул. Кремлевская, 18. E-mail: abzalov2004@mail.ru, ORCID: 0000-0003-1422-3742. Гуляков Андрей Анатольевич, старший преподаватель кафедры теории и методики физической культуры, спорта и лечебной физической культуры, Казанский (Приволжский) федеральный университет. 420008, Республика Татарстан, г. Казань, ул. Кремлевская, 18. E-mail: aguliakov@gmail.com, ORCID: 0000-0002-3010-3946. R.R. Abzalov, 2902207@mail.ru, ORCID: 0000-0003-4940-1502, N.I. Abzalov, nailabzalov@mail.ru, ORCID: 0000-0002-8428-2724, R.A. Abzalov, abzalov2004@mail.ru, ORCID: 0000-0003-1422-3742, A.A. Gulyakov, aguliakov@gmail.com, O ORCID: 0000-0002-3010-3946 Kazan (Volga region) Federal University, Kazan, Russian Federation

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200–250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses.