Nitric Oxide Donor Sodium Nitroprusside Research Articles

Efficacy of postharvest treatments with sodium nitroprusside and gibberellic acid on physio-biochemical modifications and vase life of dahlia cut flower

The goal of the current study was to evaluate the impacts of both sodium nitroprusside (SNP) and gibberellic acid (GA3) separately and in combination on the longevity of Dahlia cut flowers. Additionally, the potential physiological and biochemical changes associated with these treatments are also examined. Cut flowers treated with nitric oxide donor SNP and GA3 significantly improved all postharvest characteristics of cut flowers, including vase life and other physiological characteristics, as compared to control. Flowers treated with T15 (SNP 20 mg L-l + GA3 20 mg L-l) resulted in maximum vase life, followed by treatment T3 (SNP 20 mg-l) and minimum vase life recorded in control. Treatment T15 (SNP 20 mg L-l + GA3 20 mg L-l) shows an improvement in all biochemical activities, including superoxide dismutase, catalase, and peroxidase activity, except malondialdehyde accumulation, as compared with untreated cut flowers. Thus, SNP alone or along with GA3 as a pulsing solution could be a promising approach to improving the postharvest quality of dahlia cut flowers by influencing physiological and biochemical modifications.

THE effect of P2X7 receptor activation on functional responses of human left internal mammary artery.

The Purinoreceptor 7 (P2X7R) has become a promising drug target in many cardiovascular diseases, including coronary artery disease, since prolonged activation of P2X7R could promote vascular dysfunction, atherosclerosis, and thrombosis. Thus, we aimed to study the effects of P2X7R activation on vascular relaxation responses of the human left internal mammary artery (LIMA). Sections of redundant human LIMA were cut into 3-mm wide rings,, suspended in 20-mL organ baths containing physiologic salt solution, and attached to an isometric force transducer connected to a computer-based data acquisition system. Long-term (60min) incubation with specific P2X7R agonist Bz-ATP caused significant reductions in relaxation responses of LIMA to ATP and acetylcholine, which were reversed by selective P2X7R antagonists Brilliant Blue G or AZ11645373, whereas there were no changes in relaxation responses to endothelium-independent vasodilators isoprenaline, cAMP analog 8-Br-cAMP, and nitric oxide donor sodium nitroprusside. The impairment in relaxant responses of LIMA to endothelium-dependent vasodilators following activation of P2X7R for the long-term may contribute to postoperative LIMA vasospasm and hypertension. Modulation of P2X7R activity with selective agents may represent a new potential therapeutic approach in patients undergoing coronary artery bypass grafting surgery.

NRT2.1 mediates the reciprocal regulation of nitrate and NO/SNO in seedling leaves of Fraxinus mandshurica and Betula platyphylla

Nitric oxide (NO) and S-nitrosothiol (SNO) are signal molecules and the products of nitrogen metabolism. Nitrate (NO3−) is the main nitrogen source, and nitrate transporters (NRTs) are responsible for NO3− absorption or transport. However, the interactive effect between NO3−/NRT and NO/SNO in tree plants remains ambiguous. In the present study, 25 mmol L−1 NO3− and 1 mmol L−1 NO donor sodium nitroprusside (SNP) treatment that was conducted for 24 h enhanced NO/SNO and NO3− metabolism, whereas 2.5 mmol L−1 NO3− and 80 μmol L−1 N6022 (a compound that increases SNO content) treatment reduced them in seedling leaves of Fraxinus mandshurica and Betula platyphylla. Among the nine NRT family members examined, the gene expression level of NRT2.1 had a greater response to NO/SNO and NO3− treatment in the seedling leaves of F. mandshurica and B. platyphylla. Meanwhile, FmNRT2.1 mediated NO and SNO production in seedling leaves of F. mandshurica using Agrobacterium-mediated transient transformation. These findings shed light on the reciprocal regulation between NO3− and NO/SNO in seedlings of F. mandshurica and B. platyphylla, and NRT2.1 may act as a key regulatory hub.

Nitric Oxide Donor Sodium Nitroprusside Reduces Racemic Ketamine-But Not Esketamine-Induced Pain Relief.

The anesthetic, analgesic and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following N-methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial. Seventeen healthy volunteers were treated with 0.5 μg.kg-1.min-1 SNP or placebo during a 3-h infusion of escalating doses of racemic ketamine (total dose 140 mg) or esketamine (70 mg). Pain pressure threshold (PPT) and arterial blood samples for measurement of S- and R-ketamine and their metabolites, S- and R-norketamine, were obtained. The data were analyzed with a population pharmacokinetic-pharmacodynamic model that incorporated the measured S- and R- ketamine and S- and R-norketamine isomers as input and PPT as output to the model. The potency of the 2 formulations in increasing PPT from baseline by 100% was 0.47 ± 0.12 (median ± standard error of the estimate) nmol/mL for esketamine and 0.62 ± 0.19 nmol/mL for racemic ketamine, reflecting the 52 ± 27% lower analgesic potency of R-ketamine versus S-ketamine. Modeling showed that SNP had no effect on S-ketamine potency but abolished the R-ketamine analgesic effect. Similar observations were made for S- and R-norketamine. Since SNP had no effect on S-ketamine analgesia, we conclude that SNP interacts on R-ketamine nociceptive pathways, possibly similar to its effects on R-ketamine activated dissociation pathways.

Exogenous Sodium Nitroprusside Affects the Redox System of Wheat Roots Differentially Regulating the Activity of Antioxidant Enzymes under Short-Time Osmotic Stress.

Nitric oxide (NO) is a multifunctional signalling molecule involved in the regulation of plant ontogenesis and adaptation to different adverse environmental factors, in particular to osmotic stress. Understanding NO-induced plant protection is important for the improvement of plant stress tolerance and crop productivity under global climate changes. The root system is crucial for plant survival in a changeable environment. Damages that it experiences under water deficit conditions during the initial developmental periods seriously affect the viability of the plants. This work was devoted to the comparative analysis of the pretreatment of wheat seedlings through the root system with NO donor sodium nitroprusside (SNP) for 24 h on various parameters of redox homeostasis under exposure to osmotic stress (PEG 6000, 12%) over 0.5-24 h. The active and exhausted solutions of SNP, termed as (SNP/+NO) and (SNP/-NO), respectively, were used in this work at a concentration of 2 × 10-4 M. Using biochemistry and light microscopy methods, it has been revealed that osmotic stress caused oxidative damages and the disruption of membrane cell structures in wheat roots. PEG exposure increased the production of superoxide (O2•-), hydrogen peroxide (H2O2), malondialdehyde (MDA), and the levels of electrolyte leakage (EL) and lipid peroxidation (LPO). Stress treatment enhanced the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), the excretion of proline, and the rate of cell death and inhibited their division. Pretreatment with (SNP/+NO) decreased PEG-induced root damages by differently regulating the antioxidant enzymes under stress conditions. Thus, (SNP/+NO) pretreatment led to SOD, APX, and CAT inhibition during the first 4 h of stress and stimulated their activity after 24 h of PEG exposure when compared to SNP-untreated or (SNP/-NO)-pretreated and stress-subjected plants. Osmotic stress triggered the intense excretion of proline by roots into the external medium. Pretreatment with (SNP/+NO) in contrast with (SNP/-NO) additionally increased stress-induced proline excretion. Our results indicate that NO is able to mitigate the destructive effects of osmotic stress on the roots of wheat seedlings. However, the mechanisms of NO protective action may be different at certain periods of stress exposure.

Phosphodiesterase 9A inhibition improves aging-related increase in pulmonary vascular resistance in mice.

As individuals age, there is a gradual decline in cardiopulmonary function, often accompanied by cardiac pump dysfunction leading to increased pulmonary vascular resistance (PVR). Our study aims to investigate the changes in cardiac and pulmonary vascular function associated with aging. Additionally, we aim to explore the impact of phosphodiesterase 9A (PDE9A) inhibition, which has shown promise in treating cardiometabolic diseases, on addressing left ventricle (LV) dysfunction and elevated PVR in aging individuals. Young (3 months old) and aged (32 months old) male C57BL/6 mice were used. Aged mice were treated with the selective PDE9A inhibitor PF04447943 (1 mg/kg/day) through intraperitoneal injections for 10 days. LV function was evaluated using cardiac ultrasound, and PVR was assessed in isolated, ventilated lungs perfused under a constant flow condition. Additionally, changes in PVR were measured in response to perfusion of the endothelium-dependent agonist bradykinin or to nitric oxide (NO) donor sodium nitroprusside (SNP). PDE9A protein expression was measured by Western blots. Our results demonstrate the development of LV diastolic dysfunction and increased PVR in aged mice. The aged mice exhibited diminished decreases in PVR in response to both bradykinin and SNP compared to the young mice. Moreover, the lungs of aged mice showed an increase in PDE9A protein expression. Treatment of aged mice with PF04447943 had no significant effect on LV systolic or diastolic function. However, PF04447943 treatment normalized PVR and SNP-induced responses, though it did not affect the bradykinin response. These data demonstrate a development of LV diastolic dysfunction and increase in PVR in aged mice. We propose that inhibitors of PDE9A could represent a novel therapeutic approach to specifically prevent aging-related pulmonary dysfunction.

Sodium nitroprusside as a signal molecule for up-regulating membrane characteristics, antioxidant defense system to improve flax productivity under water stress

Water stress is a critical environmental adversity that significantly impacts the growth, development, and yield of flax plants. In this study, flax seeds were cultivated under different water irrigation requirements (WIR) (100%, 75%, and 50%) to investigate the effects of exogenously supplied nitric oxide (NO) donor sodium nitroprusside (SNP) as foliar treatments at concentrations of 0.0 ​mmol/L, 0.5 ​mmol/L, 1.0 ​mmol/L, and 2.0 ​mmol/L. Drought stress led to a significant decrease in plant growth, photosynthetic pigments, yield components such as oil and total carbohydrate percentage. It also resulted in an increase in leaf H2O2 production, lipid peroxidation levels and activities of enzymatic antioxidants including polyphenol oxidase, superoxide dismutase, and nitrate reductase enzymes. However, foliar application of SNP improved photosynthetic pigments and antioxidant defense system which mitigated the negative impact of water stress on growth and yield productivity by reducing oxidative damage caused by reactive oxygen species accumulation. The use of SNP also decreased H2O2 accumulation levels, lipid peroxidation levels, and improved membrane stability. SNP treatment at concentration of 2 ​mmol/L showed superior results compared to other concentrations with extremely significant increases observed in yield characteristics such as oil content, total carbohydrate percentages, and unsaturated fatty acids to saturated fatty acids ratio.

Understanding the interplay between strigolactone and nitric oxide in alleviating cadmium-induced toxicity in Artemisia annua

Metal stress severely limits the development and productivity of medicinal plants like A. annua. Strigolactone (SL), a relatively new plant hormone, and nitric oxide (NO) have demonstrated potential in mitigating HM-related symptoms in plants. Both SLs and NO are regulatory signals that play different roles under stressful conditions. At the moment, it is unclear how SLs and NO interact in plants under cadmium (Cd) stress. In this study, Artemisia annua was utilized to study the role and interaction of SL and NO for Cd stress tolerance. To investigate this, we undertook a detailed physiological, anatomical, and histochemical examination to determine the mechanisms by which SLs and NO reduce the effects of Cd stress on A. annua plants. Cadmium exposure hindered the growth of A. annua plants, influenced several chlorophyll fluorescence attributes, altered antioxidant enzyme activity, lowered cell viability, and caused lipid peroxidation, oxidative damage, and chloroplast ultrastructure abnormalities. A. annua plants grew better when treated with 4 μM synthetic SL analogue GR24 and 200 μM NO donor sodium nitroprusside. Meanwhile, under Cd stress, GR24 and/or SNP spray effectively boosted chlorophyll and carotenoid content, increased antioxidant enzyme activity, and elevated proline and glutathione levels. Treatment with SNP and/or GR24 improved chloroplast ultrastructure and chlorophyll fluorescence characteristics in plants under Cd-stress, resulting in better photosynthetic performance. It also reduced Cd accumulation, increased membrane permeability, and regulated stomatal behavior, resulting in enhanced stomatal conductance in Cd-stressed plants. The application of these growth regulators to plants under Cd-stress mitigated the decrease in glandular trichome dimensions and artemisinin content as observed from the HPLC results. Our results indicate that GR24 and NO, either individually or in combination, can be very effective in reducing Cd-induced damage in A. annua.

Effects of Sodium Nitroprusside on Lipopolysaccharide-Induced Inflammation and Disruption of Blood–Brain Barrier

In various neurodegenerative conditions, inflammation plays a significant role in disrupting the blood–brain barrier (BBB), contributing to disease progression. Nitric oxide (NO) emerges as a central regulator of vascular function, with a dual role in inflammation, acting as both a pro- and anti-inflammatory molecule. This study investigates the effects of the NO donor sodium nitroprusside (SNP) in protecting the BBB from lipopolysaccharide (LPS)-induced inflammation, using bEnd.3 endothelial cells as a model system. Additionally, Raw 264.7 macrophages were employed to assess the effects of LPS and SNP on their adhesion to a bEnd.3 cell monolayer. Our results show that LPS treatment induces oxidative stress, activates the JAK2/STAT3 pathway, and increases pro-inflammatory markers. SNP administration effectively mitigates ROS production and IL-6 expression, suggesting a potential anti-inflammatory role. However, SNP did not significantly alter the adhesion of Raw 264.7 cells to bEnd.3 cells induced by LPS, probably because it did not have any effect on ICAM-1 expression, although it reduced VCAM expression. Moreover, SNP did not prevent BBB disruption. This research provides new insights into the role of NO in BBB disruption induced by inflammation.

The Circulating Milieu Mediates Arterial Dysfunction with Aging: Protection by Habitual Aerobic Exercise

Age-related arterial dysfunction (aortic stiffening and endothelial dysfunction) is the key antecedent to cardiovascular diseases. Habitual aerobic exercise largely mitigates arterial dysfunction in mid-life/older (ML/O) adults; however, the mechanisms by which this occurs remain to be fully elucidated. The circulating milieu (bioactive factors in the bloodstream) shifts towards a pro-inflammatory/oxidative state with advancing age but is preserved with habitual aerobic exercise. However, it is unclear if the circulating milieu directly contributes to age-related arterial dysfunction and if habitual aerobic exercise preserves arterial function with aging, in part, by favorably modulating the circulating milieu. PURPOSE: To determine the influence of aging and habitual aerobic exercise on circulating milieu-mediated aortic stiffening and endothelial function. METHODS: Human serum was collected from healthy young (18-29 yr) and ML/O (50+ yr) men and women. Aerobic exercise status was determined by leisure-time physical activity (>60 h/wk). Aortic rings (~1 mm) and common carotid arteries were obtained from young adult (3-4 mo), intervention naïve male and female C57BL/6N mice to assess aortic stiffness and endothelial function, respectively. Arteries were exposed ex vivofor 24-48 hours to 5% sex-matched human serum from one of the following groups: young sedentary (n=9; 4F), ML/O sedentary (n=14; 7F) or ML/O habitually aerobic exercise trained (n=8; 4F). Aortic stiffness was measured as elastic modulus (a measure of intrinsic mechanical wall stiffness). Endothelial function was assessed as endothelium-dependent dilation (EDD) and endothelium-independent dilation (EID) as peak response to acetylcholine and the nitric oxide (NO) donor sodium nitroprusside, respectively. Differences were determined via one-way ANOVA. RESULTS: Aortic Stiffness. Aortic elastic modulus was higher in aorta rings incubated with ML/O sedentary serum compared to young sedentary serum (ML/O sedentary, 4912 ± 588 v. Young sedentary, 3019 ± 522 kPa; p=0.020). Compared with ML/O sedentary serum, aorta rings incubated with ML/O trained serum had lower elastic modulus (2237 ± 426 kPa, p=0.002) which was not different to aorta rings incubated with young sedentary serum (p=0.369). Endothelial Function. Peak EDD was lower in carotid arteries incubated with ML/O sedentary v. young sedentary serum (79 ± 3% v. 92 ± 2%, p=0.001). Compared with ML/O sedentary serum, incubation with ML/O trained serum evoked higher peak EDD (93 ± 1%; p=0.001) that was similar to that produced by Young sedentary serum (p=0.866). There were no group differences in peak EID (p=0.228) suggesting that circulating milieu-induced differences were endothelium-specific and were not attributable to changes in smooth muscle sensitivity to NO. CONCLUSION: These findings suggest that the circulating milieu is a key mechanism by which aging induces arterial dysfunction and by which habitual aerobic exercise training preserves arterial function with aging. F31 HL165885, R21 AG078408, K99 HL159241, K99/R00 HL151818. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Engineering of phytic acid-coated Prussian nanoparticles for combined Nitric oxide and Low-Temperature photothermal therapy of osteosarcoma

The overall survival rate for osteosarcoma (OS) has not shown any improvement over the past three decades, highlighting the persistent challenge in diagnosing and treating this disease. Nitric oxide (NO) plays a crucial role in some forms of tumor therapy. However, achieving precise and targeted release of NO remains an obstacle in anti-tumor treatment. Given this circumstance, the utilization of near infrared (NIR) laser-induced photothermal effect offers promising potential for controlled delivery of NO. In this study, we have successfully developed a therapeutic nanoparticle, PB@SNP-PA, by loading NO donor sodium nitroprusside (SNP) into Prussian blue (PB) and coating it with phytic acid (PA) for bone targeting, achieving controlled release of NO and enhancing the anti-tumor effect under NIR laser. Moreover, PB@SNP-PA significantly impairs the mitochondria of OS cells, alleviate heat tolerance induced by heat shock proteins, and mediate apoptosis as a potential anticancer mechanism. By utilizing the bisphosphonate-adsorption property of phytic acid, we have achieved bone targeting for PB@SNP-PA, which exhibits significant intra-tumoral enrichment and remarkable anti-tumor effects in vivo by inhibiting bone dissolution. These findings suggest that PB@SNP-PA functions as a unique platform for controlled NO release, proposing a novel approach for combined anti-tumor therapy involving photothermal and gas therapies.

The effect of sodium nitroprusside on the vegetative development of Aronia melanocarpa [Michx.] Elliot under in vitro conditions

Aronia is a berry fruit that has a significant amount of antioxidants. Both sexual and vegetative methods of propagation are available for aronia. Genetic diversity is present in the process of seed propagation. Therefore, clonal propagation techniques such as cuttings, basal shoots, and tissue culture are preferred. Plant tissue culture is a process that offers a high multiplication rate and the ability to produce clean plant material. This study aimed to stimulate the growth of plantlets by introducing several growth-promoting agents into the culture media. Specifically, the effects of a nitric oxide donor SNP (sodium nitroprusside) on the vegetative development of the plants were examined under in vitro conditions. Four distinct concentrations of SNP (0, 100, 200, and 300 µM) were administered to promote vegetative development. The survival rate (%), rooting rate (%), root number (per plantlet), root length (cm), leaf number (per plantlet), shoot length (cm), plant fresh weight (g), and plant dry weight (g) of the plantlets were estimated on the 60th day of growth in the nutrient medium under in vitro conditions. The survival rate was 100% for the applications of SNP at concentrations of 100 µM and 200 µM. The 0 µM treatment had the highest root number, the 100 µM treatment had the longest root, and the 200 µM treatment had the highest values for shoot length. The 0 µM treatment provided the highest values for plant fresh weight, while the 0 and 100 µM applications resulted in the highest plant dry weight values. The study suggested that an increased concentration of SNP causes a toxic effect.

NNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus

Neuronal nitric oxide synthase (nNOS, gene name Nos1) orchestrates the synthesis of nitric oxide (NO) within neurons, pivotal for diverse neural processes encompassing synaptic transmission, plasticity, neuronal excitability, learning, memory, and neurogenesis. Despite its significance, the precise regulation of nNOS activity across distinct neuronal types remains incompletely understood. Erb-b2 receptor tyrosine kinase 4 (ErbB4), selectively expressed in GABAergic interneurons and activated by its ligand neuregulin 1 (NRG1), modulates GABA release in the brain. Our investigation reveals the presence of nNOS in a subset of GABAergic interneurons expressing ErbB4. Notably, NRG1 activates nNOS via ErbB4 and its downstream phosphatidylinositol 3-kinase (PI3K), critical for NRG1-induced GABA release. Genetic removal of nNos from Erbb4-positive neurons impairs GABAergic transmission, partially rescued by the NO donor sodium nitroprusside (SNP). Intriguingly, the genetic deletion of nNos from Erbb4-positive neurons induces schizophrenia-relevant behavioral deficits, including hyperactivity, impaired sensorimotor gating, and deficient working memory and social interaction. These deficits are ameliorated by the atypical antipsychotic clozapine. This study underscores the role and regulation of nNOS within a specific subset of GABAergic interneurons, offering insights into the pathophysiological mechanisms of schizophrenia, given the association of Nrg1, Erbb4, Pi3k, and Nos1 genes with this mental disorder.

Sodium nitroprusside enhances stepping test performance and increases medium spiny neurons responsiveness to cortical inputs in a rat model of Levodopa-induced dyskinesias.

Levodopa (L-DOPA) is the classical gold standard treatment for Parkinson's disease. However, its chronic administration can lead to the development of L-DOPA-induced dyskinesias (LIDs). Dysregulation of the nitric oxide-cyclic guanosine monophosphate pathway in striatal networks has been linked to deficits in corticostriatal transmission in LIDs. This study investigated the effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on behavioural and electrophysiological outcomes in sham-operated and 6-hydroxydopamine-lesioned rats chronically treated with vehicle or L-DOPA, respectively. In sham-operated animals, systemic administration of SNP increased the spike probability of putative striatal medium spiny neurons (MSNs) in response to electrical stimulation of the primary motor cortex. In 6-hydroxydopamine-lesioned animals, SNP improved the stepping test performance without exacerbating abnormal involuntary movements. Additionally, SNP significantly increased the responsiveness of putative striatal MSNs in the dyskinetic striatum. These findings highlight the critical role of the NO signalling pathway in facilitating the responsiveness of striatal MSNs in both the intact and dyskinetic striata. The study suggests that SNP has the potential to enhance L-DOPA's effects in the stepping test without exacerbating abnormal involuntary movements, thereby offering new possibilities for optimizing Parkinson's disease therapy. In conclusion, this study highlights the involvement of the NO signalling pathway in the pathophysiology of LIDs.

Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature

BackgroundInside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation.MethodsBlood pressure lowering was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5 µg kg−1 min−1) or the Ca2+-channel blocker (nicardipine hydrochloride, 0.5 µg kg−1 min−1) for 10, and 15 to 40 min, respectively. The effect of blood pressure lowering on cerebrospinal fluid clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40 kDa horse radish peroxidase,160 kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy.ResultsNicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 24.0 ± 13.3%, while temporarily elevating intracranial pressure by 14.0 ± 7.0% and 18.2 ± 15.0%, respectively. Blood pressure lowering significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (− 66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes.ConclusionsThis is the first study showing that cerebrospinal fluid clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced cerebrospinal fluid clearance by blood pressure lowering may have therapeutic potential in diseases with dysregulated cerebrospinal fluid flow.

Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture.

Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627nm, 200lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7μmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5μM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.

Photosynthetic adaptation mechanisms of waterlogged wheat (Triticum aestivum) at flowering under exogenous nitric oxide donor application

AbstractThe effects of nitric oxide (NO) on the photosynthetic adaptation mechanisms of wheat plants in waterlogging during the flowering stage are poorly understood. Field and pot experiments using two cultivars were conducted with three treatments: waterlogging (WL), waterlogging plus NO donor sodium nitroprusside (WLsnp), and adequate water (CK). The results indicated that the WLsnp and CK treatments exhibited significantly higher 1000‐kernel weight and yield than the WL treatment because of high photosynthetic potential(P<0.05). We found that the photosynthetic performance, including photosynthetic rate (Pn), stomatal conductance (gs), mesophyll conductance (gm), carbon dioxide concentration at the carboxylation site (Cc), maximum carboxylation rate (Vcmax), maximum electron transfer rate (Jmax), actual electron transfer rate (J), actual PSII efficiency (ΦPSII) and potential maximum efficiency in PSII (Fv/Fm), was significantly improved in the WLsnp treatment compared to the WL treatment, both during waterlogging and after de‐waterlogging. Little difference was observed in the photosynthetic performance between the WLsnp and CK treatments during waterlogging for cultivar YM15 and after de‐waterlogging for cultivar YM24. Further analysis indicated that gs, gm and J were identified as key physiological indicators that synergistically regulate Pn of waterlogged wheat plants. Overall, the improvement of wheat's waterlogging resistance capacity after spraying NO is mainly related to high gs, great gm, and high J.

NO production of granulocytes associated with antibacterial immune response in Tegillarca granosa

Nitric oxide (NO) is a signaling molecule and immune effector produced by the nitric oxide synthases (NOS), which involved to various physiological processes of animals. In marine bivalves, hemocytes play important roles in antimicrobial innate immune response. Although hemocyte-derived NO has been detected in several bivalves, the immune function of hemocyte-derived NO is not well understood. Here, we investigated the antibacterial response of hemocyte-derived NO in the blood clam Tegillarca granosa. Two types of hemocytes including erythrocytes and granulocytes were isolated by Percoll density gradient centrifugation, their NO production and TgNOS expression level were analyzed. The results showed that NO was mainly produced in granulocytes and almost no detected in erythrocytes. The granulocytes showed significantly higher NO level and TgNOS expression level than the erythrocytes. And the TgNOS expression level was significantly increased in granulocytes after Vibro parahemolyticus challenge. In addition, the NO donor sodium nitroprusside (SNP) significantly increased the NO production of hemocytes to kill pathogenic bacteria. In summary, the results revealed that granulocytes-derived NO play vital roles in the antimicrobial immune response of the blood clam.

Nitric oxide-induced endoplasmic reticulum stress of Schistosoma japonicum inhibits the worm development in rats

Schistosomiasis, caused by Schistosoma spp., is a zoonotic parasitic disease affecting human health. Rattus norvegicus (rats) are a non-permissive host of Schistosoma, in which the worms cannot mature and cause typical egg granuloma. We previously demonstrated that inherent high levels of nitric oxide (NO), produced by inducible NO synthase (iNOS), is a key molecule in blocking the development of S. japonicum in rats. To further explore the mechanism of NO inhibiting S. japonicum development in rats, we performed S-nitrosocysteine proteomics of S. japonicum collected from infected rats and mice. The results suggested that S. japonicum in rats may have undergone endoplasmic reticulum (ER) stress. Interestingly, we found that the ER of S. japonicum in rats showed marked damage, while the ER of the worm in iNOS−/− rats and mice were relatively normal. Moreover, the expression of ER stress markers in S. japonicum from WT rats was significantly increased, compared with S. japonicum from iNOS−/− rats and mice. Using the NO donor sodium nitroprusside in vitro, we demonstrated that NO could induce ER stress in S. japonicum in a dose-dependent manner, and the NO-induced ER stress in S. japonicum could be inhibited by ER stress inhibitor 4-Phenyl butyric acid. We further verified that inhibiting ER stress of S. japonicum in rats promoted parasite development and survival. Furthermore, we demonstrated that NO-induced ER stress of S. japonicum was related to the efflux of Ca2+ from ER and the impairment of mitochondrial function. Collectively, these findings show that high levels of NO in rats could induce ER stress in S. japonicum by promoting the efflux of Ca2+ from ER and damaging the mitochondrial function, which block the worm development. Thus, this study further clarifies the mechanism of anti-schistosome in rats and provides potential strategies for drug development against schistosomiasis and other parasitosis.

Effect of Nitric Oxide on Browning of Stem Tip Explants of Malus sieversii

Browning is a major problem in the tissue culture of woody plants. Previous studies have shown that nitric oxide (NO) plays a role in regulating plant responses to stress, but its effect on browning in the tissue culture of Malus remains unclear. This study aimed to investigate the impact of exogenous NO donor sodium nitroprusside (SNP) on the browning of Malus sieversii stem tip explants. The results demonstrated that the addition of 50 μM SNP significantly reduced explant browning. Further analysis revealed that exogenous NO decreased the browning index (BD) and levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion radical O2−. Additionally, NO treatment increased the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX). NO treatment also enhanced the activity of phenylalanine ammonia lyase (PAL), which contributed to the accumulation of flavonoids and inhibited the activity of polyphenol oxidase (PPO) and peroxidase (POD), which are key enzymes involved in the browning process. Furthermore, 50 μM SNP significantly promoted the accumulation of non-enzymatic antioxidants such as proline (Pro), soluble sugar (SS), and soluble protein (SP). Therefore, the results suggest that NO is able to counteract excessive reactive oxygen species (ROS) damage by enhancing both the enzymatic and non-enzymatic antioxidant systems, resulting in a reduction in browning in stem tip explants. Consequently, an improvement in the in vitro propagation efficiency of Malus sieversii shoot tip explants can be achieved.