Combination Of Sodium Nitroprusside Research Articles

Combination of Sodium Nitroprusside and Controlled Atmosphere Maintains Postharvest Quality of Chestnuts through Enhancement of Antioxidant Capacity.

The purpose of this study was to clarify the effect of CA (controlled atmosphere, 2-3% O2 + 3% CO2) and NO (nitric oxide, generated by 0.4 nM sodium nitroprusside), alone or combined (CA + NO), on the physio-chemical properties, enzyme activities and antioxidant capacities of chestnuts during storage at 0 °C for 180 d. Compared with control (CT), CA and CA+NO both improved the storage quality of the samples, but only CA resulted in more ethanol production. Moreover, these improvements were further enhanced and ethanol synthesis was inhibited by the addition of NO. A spectrometer was used to assess the production of phenolic content (TPC) and activities of phenylalanine ammonia-lyase (PAL), superoxide dismutas (SOD), peroxidase (POD), catalase (CAT) and polyphenol oxidase (PPO) as influenced by CA or CA+NO treatments. Higher TPC, PAL, SOD, POD, CAT, and lower PPO were observed in CA alone, and more so in the combination with NO group. The increased antioxidant production and enhanced antioxidant activities contributed to scavenging reactive oxygen species (ROS) and reducing malondialdehyde (MDA). This study unveiled the correlations and differences between the effects of CA and CA+NO on storage quality, providing valuable insights into postharvest preservation and suggesting that the combination (CA+NO) was more beneficial for quality maintenance in chestnuts.

Comparison of Clinical Efficacy of Sodium Nitroprusside and Urapidil in the Treatment of Acute Hypertensive Cerebral Hemorrhage.

This paper mainly studies the clinical efficacy of sodium nitroprusside and urapidil in the treatment of acute hypertensive intracerebral hemorrhage and analyzes the brain CT image detection based on a deep learning algorithm. A total of 132 cases of acute hypertension admitted to XXX hospital from XX 2019 to XX 2020 were retrospectively analyzed. The diseases of all patients were clinically confirmed, and patients were divided into groups according to the differences in treatment methods. Urapidil was used for group 1; sodium nitroprusside was used for group 2; and urapidil combined with sodium nitroprusside was used for group 3. A convolutional neural network in deep learning is used to construct intelligent processing to classify brain CT images of patients. The network performance of AlexNet, GoogLeNet, and CNN3 is predicted. The results show that GoogLeNet has the highest prediction accuracy of 0.83, followed by AlexNet with 0.80 and CNN3 with 0.74. The results of the performance parameter curve show that the GoogLeNet has the highest performance parameter of 0.89, followed by AlexNet and CNN3 network. The performance parameter curve of machine learning is above 0.80. After five weeks of drug treatment, the hematoma volume was (3.8 ± 2.6) mL in group1, (7.6 ± 2.8) mL in group 2, and (2.8 ± 1.5) mL in group 3. After 5 days of treatment, the patients' heart rate changed compared with before treatment. Compared with group 2, there were significant differences between groups 1 and 3 (P < 0.01), indicating that the therapeutic effect of the combination group was significantly better than that of the other groups alone. In summary, the combination of sodium nitroprusside and urapidil has a significantly better effect than that of urapidil alone. A convolutional neural network based on deep learning improves the recognition accuracy of medical images.

Combination of nitrate and sodium nitroprusside dosing for sulfide control with low carbon source loss in sewer biofilm reactors

Nitrate has been widely used in sewer systems for sulfide control. However, significant chemical consumption and the loss of carbon source were observed in previous studies. To find a feasible and cost-effective control strategy of the sulfide control, the effect of nitrate combined with sodium nitroprusside (SNP) dosage strategy was tested in lab-scale sewer biofilm reactors. Results showed that nitrate and SNP were strongly synergistic, with 30 mg N/L nitrate and 20 mg/L SNP being sufficient for sulfide control in this study. While large amount of nitrate alone (100 mg N/L) is required to achieve the same sulfide control effectiveness. Meanwhile, the nitrate combined with SNP could reduce the organic carbon source loss by 80%. Additionally, the high-throughput sequencing results showed that the relative abundance of autotrophic, nitrate reducing-sulfide oxidizing bacteria genera (a-NR-SOB) such as Arcobacter and Sulfurimonas was increased by around 18%, while the heterotrophic, nitrate-reducing bacteria (hNRB) such as Thauera was substantially reduced. It demonstrated that the sulfide control was mainly due to the a-NR-SOB activity under the nitrate and SNP dosing strategy. The microbial functional prediction further revealed that nitrate and SNP promoted the dissimilatory nitrate reduction process which utilizes sulfide as an effective electron donor. Moreover, economic assessment indicated that using the combination of nitrate and SNP for sulfide control in sewers would lower the chemical costs by approximately 35% compared with only nitrate addition.

Interaction of Auxin and Nitric Oxide Improved Photosynthetic Efficiency and Antioxidant System of Brassica juncea Plants Under Salt Stress

It is known that auxin and nitric oxide have the ability to ameliorate various abiotic stresses in plants individually. However, their interactive effects on the stress generated by salt in plants are not reported yet. Therefore, the present study was conducted to explore the effectiveness of sodium nitroprusside (SNP), a donor of nitric oxide and IAA (Indole acetic acid) individually and in combination on the photosynthetic efficiency, antioxidative enzyme activities, and plant biomass under salt stress. Twenty-five-day-old plants were exposed to SNP and IAA individually and in combination for 5 days continuously, and it was found that both SNP and IAA showed almost similar response at 30 and 45 days of old plants and increased studied parameters over their respective controls. However, the interactive effect of both SNP and IAA excelled over the individual response of SNP and IAA. On the other hand, the presence of salt in soil significantly decreased the parameters studied. Furthermore, stress generated by NaCl was overcome by the exogenous application of SNP, IAA alone as well as in combination at both the stages of samplings. However, the combination of IAA and SNP was more effective at 45 DAS where the value of plant biomass and photosynthetic efficiency was more in comparison to control plants. The level of antioxidant enzymes and proline was further enhanced by SNP and IAA and maximum values were reported in the plants received both SNP and IAA under NaCl stress. This enhanced antioxidant system and proline accumulation could ameliorate the stress induced by NaCl in plants that was reflected by the improved plant biomass, and photosynthetic efficiency in comparison to control plants.

Regulatory Role of Nitric Oxide in Development and Hatching of Mouse Blastocysts

To determine the regulatory role and mechanism of nitric oxide (NO) in the development and hatching of mouse blastocysts. The Kunming female mice were superovulated and then mated with mature male mice. On the day 2.5 of their pregnancy, morulae were flushed from their uterine horns with culture media. Morulae were cultured in different concentrations of N-nitro-L arginine methyl ester (L-NAME), sodium nitroprusside (SNP), or the combination of L-NAME and SNP in culture media for 48 hours. The development and hatching of blastocysts were examined on day 4 and day 5 and the total numbers of blastocyst cells and cysteinyl aspartate specific proteinase 3 (caspase 3) were observed under confocal laser scanning microscope. With the increase of the concentration of L-NAME or SNP, the hatching rate of blastocysts and the total number of blastocyst cells were significantly reduced. The addition of 10 nmol/L SNP in culture media with 5 mmol/L L-NAME significantly increased the development of blastocysts and promoted hatching of blastocysts. However, with increase of SNP concentration in culture media with 5 mmol/L L-NAME, the development and hatching rates of blastocysts were significantly decreased. L-NAME had no obvious effect on the expression of active caspase 3 in blastocyst cells. However,when being above 500 nmol/L,SNP significantly increased the expression of caspase 3 in blastocyst cells. NO plays an important role in development and hatching of mouse blastocysts. Excessively high or low NO can damage the division of blastomeres, resulting in the failure of the blastocyst development and hatching. Also, excessively high NO can lead to the apoptosis of the blastocyst cells.

Abstract 249: Sodium Nitroprusside Combined with Intrathoracic Pressure Regulation Increases Neurologically Favorable 24-Hour Survival in a Porcine Model of Prolonged Ventricular Fibrillation

Introduction: Use of epinephrine and standard (S) CPR has not been shown to improve neurologically-sound survival after cardiac arrest. Treatment with the potent vasodilator sodium nitroprusside (SNP) improves neurologically intact survival rates in animals when combined with abdominal compression, active compression decompression (ACD) CPR, and an impedance threshold device (ITD). We recently observed that SNP combined with ACD-CPR and a new intrathoracic pressure regulator (IPR), which provides continuous negative intrathoracic pressure after each positive pressure ventilation, increases blood flow to the heart and brain in the absence of epinephrine or abdominal compression. We hypothesized that this combination of SNP plus ACD CPR plus IPR (S-A-I) would improve 24h survival with favorable neurologic function compared with S-CPR. Method: After 12 minutes of untreated ventricular fibrillation (VF), 14 pigs received 3 minutes of S-CPR and were then randomized to a) a bolus of epinephrine (0.05mcg/kg), 2 more minutes of S-CPR and up to 3 defibrillation shocks or b) S-A-I and up to 3 shocks 2 minutes later. All resuscitated animals received therapeutic hypothermia for 4 hours. The primary endpoint was favorable neurologic outcome 24h after resuscitation defined by a Cerebral Performance Category score ≤ 2 (CPC with 1 for no deficit and 5 as dead or unable to resuscitate) as determined by a blinded veterinarian. Hemodynamic parameters and left ventricular ejection fraction were recorded. Data are presented as mean±SEM. Results: At 24 hours, 0/7 pigs in the S-CPR group vs. 5/7 pigs in S-A-I had favorable outcome (p=0.02). One pig survived 24 hours in the S-CPR group with a CPC of 4 vs. 5 in the S-A-I group with a CPC of 1.4±0.2. Carotid blood flow and ETCO2 were higher with S-A-I_vs. S-CPR and epinephrine (127±32 vs. 22±4 ml/min, p=0.005, and 46±5 vs. 22±3 mmHg, respectively, p=0.001). Conclusion: After prolonged VF in pigs, treatment with the combination of ACD CPR, an intrathoracic pressure regulator and SNP, in the absence of epinephrine, significantly increased carotid flow, ETCO2 levels, and neurologically-favorable 24 hour survival rates compared with S-CPR and epinephrine. This novel and promising approach should be considered for a Phase 1 human trial.

外源SA和NO对NaCl胁迫下番茄幼苗生长、光合及离子分布的影响

以番茄（<em>Lycopersicon esculentum</em> Mill.）品种‘秦丰保冠’为试材，采用营养液培养法，研究单独和复配施用外源水杨酸（SA）、一氧化氮（NO）供体硝普钠（SNP）对100mmol/L NaCl胁迫下番茄幼苗生长、光合及离子分布的影响。结果表明：（1）单独和复配外施SA、SNP均能有效抑制NaCl胁迫下番茄幼苗叶片光合色素（Chla、Chlb、Chla+b和Car）含量、Chla/b值、净光合速率（<em>P</em>_n）、蒸腾速率（<em>T</em>_r）、气孔导度（<em>G</em>_s）、瞬时水分利用效率（WUE_t）、表观光能利用效率（LUE_app）和表观CO₂利用效率（CUE_app）的下降及Car/Chla+b值和胞间CO₂浓度（<em>C</em>_i）的升高，并以SA 和SNP复配处理效果最明显。（2）NaCl胁迫下，外源SA、SNP单独和复配处理的番茄幼苗各器官（叶、茎和根）中Cl^-、Na⁺含量和Na⁺/K⁺、Na⁺/Ca²⁺、Na⁺/Mg²⁺值显著降低，而K⁺、Ca²⁺和Mg²⁺的含量却不同程度提高，其中以SA 和SNP复配处理效果最好。（3）单独和复配外施SA、SNP均能有效减轻NaCl胁迫对番茄幼苗生长的抑制作用，并促进各器官生物量的积累和壮苗的形成，且以SA 和SNP复配处理效果更佳。研究表明，复配外施SA和SNP在诱导番茄幼苗提高抗（耐）盐能力方面具有协同增效作用。

Central nervous system toxicity of sodium nitroprusside in treatment of patients with aortic dissection

This study examined the sodium nitroprusside (SNP) toxicity to central nervous system (CNS) in treatment of patients with aortic dissection (AD). The medical records of 191 AD patients who were admitted to Tongji Hospital, China, from Jan. 1998 to Feb. 2009 were retrospectively analyzed. There were 140 cases of hypertension (73.3%) and 13 cases of Marfan syndrome (6.8%) among the 191 AD patients. A total of 157 patients were given SNP treatment. The toxic reactions of CNS occurred in 18 subjects (11.5%). Most of the adverse reactions occurred on the fifth day following SNP injection. SNP infusion rate was significantly higher in patients who developed CNS toxicity. It was suggested that systemic hypertension is the most common predisposing factor for AD. The combination of SNP with a β-receptor blocker is a medical therapy commonly used in patients with AD. Cyanide and thiocyanate toxicity from SNP treatment is always the consequence of prolonged drug infusion or relatively high dose administration.

Influence of Nitric Oxide on Steroid Synthesis, Growth and Apoptosis of Buffalo (Bubalus bubalis) Granulosa Cells In vitro

Objective of this study was to examine the effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor on steroid synthesis, growth and apoptosis of buffalo granulosa cells (GCs) in vitro. Follicular fluid of antral follicles (3-5 mm diameter) was aspirated and GCs were cultured in 0 (control), , , , of SNP for 48 h. To evaluate whether this effect was reversible, GCs were cultured in presence of SNP+1.0 mM -nitro-L-arginine methyl ester (L-NAME) a NO synthase (NOS) inhibitor or hemoglobin (Hb, ) as NO scavenger. Nitrate/nitrite concentration was evaluated by Griess method, progesterone and estradiol concentrations by RIA and apoptosis by TUNEL assay. SNP (, , ) significantly (p SNP induced the progesterone synthesis and stimulated GCs to develop into a uniform monolayer. Combination of SNP M+L-NAME strengthened the inhibitory effect while, SNP+Hb together reversed these inhibitory effects. In conclusion, SNP at greater concentrations (, and ) has a cytotoxic effect and it may lead to cell death whereas, at a lower concentration () induced progesterone synthesis and growth of GCs. These findings have important implications that NOS derived NO are involved at physiological level during growth and development of buffalo GCs which regulates the steroidogenesis, growth and apoptosis.

NO-induced activation of cyclic GMP-dependent pathway down regulates ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) protein in rat C6 glioma

In rat C6 glioma cells, the ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1), a modulator of purinergic receptor signaling, is down regulated after an increase in intracellular cAMP by addition of dibutyryl cAMP, a membrane-permeable cAMP-analog, or by activation of the β-adrenoceptor receptor with (−)-isoproterenol (Aerts et al., 2011, Eur. J. Pharmacol. 654, 1–9). In this communication we studied the effect of nitric oxide (NO)/cGMP, a pathway also affecting purinergic receptor signaling, on the level of NPP1 protein. Sodium nitroprusside (SNP), a NO donor, reduces NPP1 protein in a dose-dependent manner. A combination of SNP and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, demonstrated that NO-dependent down regulation of NPP1 was caused by NO-sensitive guanylyl cyclase. Treatment with Rp- pCPT-cGMPS, an inhibitor of protein kinase G (PKG), showed that PKG is not involved in the down regulation of NPP1. In addition, we have shown that the cAMP- and cGMP-dependent decrease in NPP1 expression is unrelated. These results indicate that NO/cGMP regulates the level of NPP1 protein by a pathway that differs from the cAMP-induced decrease in NPP1.

Influence of nitric oxide onin vitrogrowth, survival, steroidogenesis, and apoptosis of follicle stimulating hormone stimulated buffalo (Bubalus bubalis) preantral follicles

Effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on in vitro survival, growth, steroidogenesis, and apoptosis of buffalo preantral follicles (PFs) was investigated. PFs (200~250 µm) were isolated by micro-dissection and cultured in 0 (control), 10-3, 10-5, 10-7, and 10-9 M SNP. To examine the reversible effect of SNP, PFs were cultured with 10-5 M SNP + 1 mM Nω-nitro-L-arginine methyl ester (L-NAME) or 1.0 µg hemoglobin (Hb). The results showed that greater concentrations of SNP (10-3, 10-5, 10-7 M) inhibited (p < 0.05) FSH-induced survival, growth, antrum formation, estradiol production, and oocyte apoptosis in a dose-dependent manner. However, a lower dose of SNP (10-9 M) significantly stimulated (p < 0.05) the survival, growth, antrum formation, follicular oocyte maturation, and stimulated progesterone secretion compared to the control. A combination of SNP + L-NAME promoted the inhibitor effect of SNP while a SNP + Hb combination reversed this effect. Nitrate and nitrite concentrations in the culture medium increased (p < 0.05) in a dose-dependent manner according to SNP concentration in the culture medium. At higher concentrations, SNP had a cytotoxic effect leading to follicular oocyte apoptosis whereas lower concentrations have stimulatory effects. In conclusion, NO exerts a dual effect on its development of buffalo PFs depending on the concentration in the culture medium.

Interaction of the HMG-CoA Reductase Inhibitor Lovastatin and Nitric Oxide in Cardiomyocyte Cell Death

Aim: The objective of this study was to examine the interaction ofa 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) with a nitric oxide (NO) donor from the perspective of the impact on cardiomyocyte cell viability. Methods: Embryonic chick cardiomyocytes in culture were treated with a wide range of concentrations of sodium nitroprusside (SNP), which releases NO and also generates toxic reactive nitrogen species. SNP was combined with the HMG-CoA reductase inhibitor lovastatin and cell viability was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Results: SNP and lovastatin each produced a significant (p < 0.01) concentration-dependent increase in cell death. Using SNP concentrations at or below the ED₅₀, SNP (0.01, 0.1 or 0.5 mmol/l) increased the amount of cell death when combined with lovastatin (1, 10, 50 and 100 µmol/l). At lovastatin concentrations of 50 µmol/l and less, the amount of cell death was consistently similar to the arithmetic sum of SNP and lovastatin, suggesting that there was an additive and not synergistic relationship between SNP and lovastatin. In combination with lovastatin (100 µmol/l), however, the amount of cell death was consistently lower than the calculated expected value and suggested saturation of a common mechanism. The combination of SNP and lovastatin produced the characteristic microscopic changes of apoptosis. Considering that both SNP and lovastatin can activate caspase-3, cells were treated with the caspase-3 inhibitor Ac-DEVD-CHO. This inhibitor produced a significant (p < 0.05) and consistent 30% reduction in the amount of cell death induced by SNP and lovastatin. Conclusion: These data suggest that the cardiomyocyte toxicity from NO continues to be evident uninterrupted by and not accentuated by the presence of an HMG-CoA inhibitor. The cardiac adverse effect of each of these agents utilizes a common pathway involving caspase-3 so that their cardiotoxicity can be blunted by a caspase-3 inhibitor.

Nitric Oxide Potentiates Oligosaccharide‐induced Artemisinin Production in Artemisia annua Hairy Roots

The purpose of the present study was to characterize the generation of nitric oxide (NO) in Artemisia annua roots induced by an oligosaccharide elicitor (OE) from Fusarium oxysporum mycelium and the potentiation role of NO in the elicitation of artemisinin accumulation. The OE (0.3 mg total sugar/mL) induced a rapid production of NO in cultures, which exhibited a biphasic time course, reaching the first plateau within 1.5 h and the second within 8 h of OE treatment. Artemisinin content in 20-day-old hairy roots was increased from 0.7 mg/g dry wt to 1.3 mg/g dry wt by using the OE treatment for 4 d. In the absence of OE, the NO donor sodium nitroprusside (SNP) at 10, 50 microM and 100 microM enhanced the growth of hairy roots, but had no effect on artemisinin synthesis. The combination of SNP with OE increased artemisinin content from 1.2 mg/g dry wt to 2.2 mg/g dry wt, whereas the maximum production of artemisinin in cultures was 28.5 mg/L, a twofold increase over the OE treatment alone. The effects of SNP on the OE-induced artemisinin were suppressed strongly by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). The results suggest that NO can strongly potentiate elicitor-induced artemisinin synthesis in A. annua hairy roots.

Modulation of the inflammatory response to histamine by terbutaline and sodium nitroprusside in guinea‐pig skin

We measured the microvascular response (vasodilatation and plasma exudation) to skin prick provocations with histamine, terbutaline, sodium nitroprusside (SNP) and the combinations of terbutaline and histamine as well as SNP and histamine in guinea-pig skin. The response was measured by external detection of beta radiation from transferrin labelled with (113m)In. Histamine induced a moderate microvascular response. Terbutaline alone induced a smaller response, probably reflecting vasodilatation. When added to histamine, terbutaline significantly reduced the microvascular response to histamine. The response to histamine, SNP and the combination of histamine and SNP were all similar. We conclude that the anti-inflammatory effect of terbutaline can be readily measured with this technique. We found no indication of a pro-inflammatory effect of SNP when combined with histamine. Rather, the lack of additive effect may suggest an anti-inflammatory effect of SNP on the response to histamine.

Therapeutic concentrations of propofol protects mouse macrophages from nitric oxide-induced cell death and apoptosis.

To evaluate the potential effect of a clinically relevant concentration of propofol (PPF) on cell viability and nitric oxide-induced macrophage apoptosis. Mouse macrophages (cell line Raw 264.7) were cultured and incubated with a nitric oxide donor sodium nitroprusside (SNP), PPF, and a combination of PPF and SNP for one, six and 24 hr. Cell viability was determined by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were determined by analyzing the percentages of sub-G1 phase in macrophages. The amounts of nitric oxide were assayed. The amounts of nitric oxide in macrophages were increased with time when incubated with SNP (P < 0.05). Simultaneously, SNP caused cell death of macrophages in a concentration-and time-dependent manner (P < 0.05). PPF per se did not alter the amount of basal and SNP-provided nitric oxide in macrophages. A therapeutic concentration of PPF (30 microM) exhibited no cytotoxicity. After incubation with SNP for one and six hours, PPF could completely or partially block nitric oxide-induced cell death, respectively (P < 0.05). Administration of SNP to macrophages resulted in a time-dependent pattern of increase of apoptotic cells (P < 0.05). Similar to the results of the cell viability analyses, PPF was able to protect macrophages from nitric oxide-induced apoptosis in one and six hour-treated groups (P < 0.05) but not in the 24 hr treated group. PPF, at a therapeutic concentration, can protect mouse macrophages in vitro from nitric oxide-induced cell apoptosis as well as cell death.

CAMP inhibits IP(3)-dependent Ca(2+) release by preferential activation of cGMP-primed PKG.

The singular effects and interplay of cAMP- and cGMP-dependent protein kinase (PKA and PKG) on Ca(2+) mobilization were examined in dispersed smooth muscle cells. In permeabilized muscle cells, exogenous cAMP and cGMP inhibited inositol 1,4,5-trisphosphate (IP(3))-induced Ca(2+) release and muscle contraction via PKA and PKG, respectively. A combination of cAMP and cGMP caused synergistic inhibition that was exclusively mediated by PKG and attenuated by PKA. In intact muscle cells, low concentrations (10 nM) of isoproterenol and sodium nitroprusside (SNP) inhibited agonist-induced, IP(3)-dependent Ca(2+) release and muscle contraction via PKA and PKG, respectively. A combination of isoproterenol and SNP increased PKA and PKG activities: the increase in PKA activity reflected inhibition of phosphodiesterase 3 activity by cGMP, whereas the increase in PKG activity reflected activation of cGMP-primed PKG by cAMP. Inhibition of Ca(2+) release and muscle contraction by the combination of isoproterenol and SNP was preferentially mediated by PKG. In light of studies showing that PKG phosphorylates the IP(3) receptor in intact and permeabilized muscle cells, whereas PKA phosphorylates the receptor in permeabilized cells only, the results imply that inhibition of IP(3)-induced Ca(2+) release is mediated exclusively by PKG. The effect of PKA on agonist-induced Ca(2+) release probably reflects inhibition of IP(3) formation.

YC-1 potentiates nitric oxide-induced relaxation in guinea-pig trachea.

1. The effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) on tension, levels of cyclic GMP and cyclic AMP were investigated in guinea-pig trachea. We especially studied the combined effect of YC-1 with exogenous or endogenous nitric oxide on these parameters. 2. YC-1 at the concentration 3 or 10 microM, which caused only minor effect by itself, elicited concentration-dependent potentiation of sodium nitroprusside (SNP)-induced tracheal relaxation. This relaxation of YC-1 with SNP was reversed by ODQ. 3. Relaxant responses to electric field stimulation (EFS) in the presence of indomethacin, atropine, guanethidine, alpha-chymotrypsin and histamine were also markedly increased by YC-1 (10 microM). In the presence of L-NAME or ODQ, the relaxant effects to EFS were attenuated and the following addition of YC-1 did not further enhance relaxation. 4. YC-1 (10 microM) or SNP (0.3 microM) alone did not induce significant elevation of cyclic GMP levels in the presence of IBMX, whereas simultaneous application of both compounds markedly elevated the cyclic GMP accumulation. In contrast, the cyclic AMP levels were not altered even at the combination of YC-1 and SNP. Additionally, YC-1 also affected cyclic GMP metabolism, since it inhibited the activity of phosphodiesterase type V in human platelets. 5. YC-1 (30 microM) did not scavenge superoxide anion and had no effect on the removal of superoxide anion by superoxide dismutase in a xanthine/xanthine oxidase system. 6. In conclusion, these results indicate that although YC-1 elicits negligible relaxation of guinea-pig trachea by itself, it can potentiate the relaxant responses of exogenous or endogenous NO. This synergistic response of YC-1 is via the elevation of cyclic GMP contents.

Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors

To gain insights into the cellular responses evoked by nitric oxide (NO), we have studied the effects of NO donors with distinct chemistries on the expression of heme oxygenase-1 mRNA by northern blot analysis. The expression levels of heme oxygenase-1 mRNA were increased significantly in DLD-1 human colorectal adenocarcinoma cells by treatment with each of three NO donors: sodium nitroprusside (SNP), S-nitroso- l-glutathione (GSNO), and 3-morpholinosydnonimine (SIN-1). A combination of SIN-1 plus SNP or GSNO additively increased heme oxygenase-1 mRNA expression, whereas synergistic induction was seen with SNP plus GSNO. The SNP-mediated induction was not affected noticeably by extracellular superoxide dismutase, catalase, or mannitol, while the induction by SIN-1 was attenuated by superoxide dismutase. Thus, the SNP-mediated induction of heme oxygenase-1 mRNA expression may be independent of reactive oxygen species, and the induction by SIN-1 is mediated partly by peroxynitrite, which is generated by immediate reaction of NO and superoxide anion. Transient transfection assays suggested that treatment with SNP, but not with GSNO or SIN-1, increased the expression of a reporter gene through a cis-acting element, including the cadmium-responsive element, of the human heme oxygenase-1 gene. These results suggest that SNP induces heme oxygenase-1 mRNA expression through a mechanism different from that for GSNO or SIN-1. We therefore propose that induction of heme oxygenase-1 represents a common cellular response in sensing the signals evoked by distinct NO donors.

Effects of nitric oxide on chemotaxis and endotoxin-induced interleukin-8 production in human neutrophils.

The effects of nitric oxide (NO) on human neutrophil chemotactic responses and release of interleukin (IL)-8 was studied. Neutrophils exposed to chemoattractants (IL-8, FMLP, leukotriene B4, and C5a) failed to show increases in intracellular guanosine 3',5'-cyclic monophosphate (cGMP), an indicator of NO production. Although NO increased cGMP in neutrophils, neither of two NO donors (sodium nitroprusside and 3-morpholino-sydonimine) nor a NO synthase inhibitor (N omega-nitro-L-arginine) altered FMLP- or IL-8-elicited neutrophil chemotaxis (P > .25 for all). However, lipopolysaccharide-induced IL-8 production was increased in a dose-dependent manner by a combination of sodium nitroprusside and N-acetylcysteine (P = .03) or by S-nitrosoglutathione (P = .004). NO-augmented IL-8 release was not reproduced by treating neutrophils with dibutyryl-cGMP. Up-regulation of IL-8 release by NO was associated with increased IL-8 mRNA levels (P = .009). These data suggest that NO does not directly affect neutrophil chemotaxis but may indirectly alter chemotactic responses by increasing IL-8 production via a cGMP-independent pathway.

Sodium Nitroprusside

Sodium Nitroprusside