Possible Roles Of Nitric Oxide Research Articles

NO Is Not the Same as GSNO in the Regulation of Fe Deficiency Responses by Dicot Plants.

Iron (Fe) is abundant in soils but with a poor availability for plants, especially in calcareous soils. To favor its acquisition, plants develop morphological and physiological responses, mainly in their roots, known as Fe deficiency responses. In dicot plants, the regulation of these responses is not totally known, but some hormones and signaling molecules, such as auxin, ethylene, glutathione (GSH), nitric oxide (NO) and S-nitrosoglutathione (GSNO), have been involved in their activation. Most of these substances, including auxin, ethylene, GSH and NO, increase their production in Fe-deficient roots while GSNO, derived from GSH and NO, decreases its content. This paradoxical result could be explained with the increased expression and activity in Fe-deficient roots of the GSNO reductase (GSNOR) enzyme, which decomposes GSNO to oxidized glutathione (GSSG) and NH3. The fact that NO content increases while GSNO decreases in Fe-deficient roots suggests that NO and GSNO do not play the same role in the regulation of Fe deficiency responses. This review is an update of the results supporting a role for NO, GSNO and GSNOR in the regulation of Fe deficiency responses. The possible roles of NO and GSNO are discussed by taking into account their mode of action through post-translational modifications, such as S-nitrosylation, and through their interactions with the hormones auxin and ethylene, directly related to the activation of morphological and physiological responses to Fe deficiency in dicot plants.

Effects of Nitric Oxide Application on Antioxidant Enzyme Activities of Pepper Plants under Drought Stress

The purpose of the study was to determine the relationship between the messenger molecule Nitric oxide (NO) and antioxidative enzyme (SOD: Superoxide Dismutase; CAT: Catalase; APX: Ascorbate Peroxidase) activities in some metabolic changes that occur under the effect of drought stress in plants, to determine the possible roles of Nitric Oxide and to obtain complementary information. The experiment conducted in a controlled environment, and plant were cultured in containers containing Hoagland nutrient solution. For drought stress application, 10% Polyethylene Glycol (PEG 6000) was added to the nutrient solution, which is equivalent to -0.40 MPa osmotic potential. Before the drought stress is applied, pepper seedlings of Demre cv were pre-treated with different doses of Sodium Nitroprusside (SNP) and Carboxy-PTIO (potassium salt) (cPTIO) (SNP 0.01, SNP 1, SNP 100 and SNP 0.01 + cPTIO, SNP + cPTIO, SNP 100+ cPTIO). On the 10th day of the drought application, the growth parameters of the plants; the plant fresh weights and their Antioxidative Enzyme Activities (SOD, CAT, APX) were determined. In terms of plant growth parameters, both plant growth and antioxidant anzyme activities of plants pretreated with 0.01 and 1 doses of SNP were lower than the high dose of SNP and the PEG application without pretreatment. The reason for the low enzyme activities in these applications can be attributed to factors such as the excess accumulation of organic acids such as proline in the cells of the plants and the decrease in H2O2 and O-2 levels in the presence of SNP.

Treated with Nitric Oxide Pepper Plant under Drought Stress Proline, Protein Determination of Relative Water Content and Chlorophyll amount

The aim of this study was to determine the possible roles of NO (Nitric Oxide) which has the characteristic of messenger molecule in some metabolic changes under the effect of drought stress in plants and to determine the relationship between proline, protein, proportional water content and chlorophyll amounts. The study was carried out under controlled conditions in 16/8 hour light / dark photoperiod, 25 0C and 70% humid climate room. The plants were cultured in containers containing Hoagland nutrient solution. For application of drought stress, 10% Polyethylene Glycol (PEG 6000) was added to the nutrient solution which corresponds to the osmotic potential of -0.40 MPa. Before applying drought stress, different doses of pepper seedlings sodium nitroprusside (SNP) and potassium salt (carboxy-PTIO) were applied externally after SNP 0.01, SNP 1, SNP 100 and SNP 0.01 + cPTIO, SNP 1 + cPTIO, SNP. 100 + cPTIO. Sampling was performed on the 10th day of drought. After the total plant weights were measured, Proline, Protein, Proportional Water Content (OSI), and Chlorophyll content of the leaves of pepper plants were examined in order to clarify the damage mechanism of drought stress and the effect of stress on applications. In terms of total plant weight, it was observed that the growth and growth of pretreated plants were better with 0.01 and 1 doses of SNP and an increase in Proline, Protein, OSI and Chlorophyll amounts. Keywords: Pepper, Capsicum annum, carboxy-PTIO, Drought stress, Nitric oxide, Proline, Protein, Chlorophyll, SNP DOI: 10.7176/JSTR/5-10-06

Effects of endothelin and nitric oxide on cardiac muscle functions in experimental septic shock model.

We aimed to investigate the possible roles of nitric oxide (NO) and endothelin on the changes of cardiac muscle function in both hyper- and hypodynamic septic shock periods. Cecal ligation and puncture was performed in 50 Wistar albino rats to induce septic shock. Changes in atrium and right ventricle papillary muscle contractions, atrium beat rate, adrenergic and cholinergic responses in these tissues were evaluated in vitro. Atrium beat rate increased in hypodynamic period (p < 0.001) that was reversed by bosentan (p < 0.001) and N(G)-nitro-L-arginine methylester (L-NAME; p < 0.05). Atrium contractions decreased in both hyper- and hypodynamic periods (p < 0.001) that were partially ameliorated by bosentan in both periods (p < 0.01) and only in hypodynamic period by L-NAME (p < 0.001). L-NAME increased papillary muscle contractions in both periods (p < 0.01), but bosentan increased it only in hyperdynamic period (p < 0.01). Bosentan and L-NAME increased potency of isoproterenol on atrium beat rate in both periods and increased carbachol potency on atrium beat rate and atrium contraction amplitude only in hypodynamic period. Bosentan increased atrium contraction response to isoproterenol in hypodynamic period (p < 0.05). Papillary muscle contraction response to isoproterenol increased in hypodynamic period (p < 0.05). L-NAME increased papillary muscle contraction response to carbachol in both periods (p < 0.01, p < 0.05, respectively). These results show that NO and endothelin may play a role in positive inotropic and negative chronotropic effects for atrium in septic shock. Bosentan and L-NAME may change potency and efficacy of isoproterenol and carbachol via upregulation of adrenergic and cholinergic receptors and/or through post receptor factors.

Nitric oxide in chromatic body patterning elements of Sepia officinalis

The spectacular variety of body coloration patterns in Sepia officinalis reflects the concerted activity of the skin chromatic elements, chromatophores, leucophores and iridophores. Recent studies have revealed that nitric oxide is an important messenger in the long term maintenance of the body coloration, inducing chromatophore expansion downstream glutamate activation. Herein we describe the presence of nitric oxide synthase and nitric oxide synthesis in isolated juvenile iridophores in Sepia. The possible roles of nitric oxide in the complex mechanisms leading to body coloration patterns in cephalopods are an important focus for ongoing and future studies.

Apoptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocytes: Possible Roles of Nitric Oxide and the Thioredoxin 1

Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. The impaired apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is pivotal in this process. However, the molecular mechanisms responsible for the reduced apoptosis are not fully understood. Both nitric oxide and thioredoxin 1 as two important mediators are widely investigated in the pathogenesis of rheumatoid arthritis. Interestingly, studies have showed that thioredoxin 1 may serve as a master regulator of S-nitrosylation of caspase-3 to fine-tune apoptosis in vivo. Thus, it is anticipated that further investigations on the role of thioredoxin 1 in the S-nitrosylation and denitrosylation of caspase-3 in RA-FLS will likely provide a novel understanding of mechanisms implicated in the impaired apoptosis of RA-FLS. In this paper, we will provide an overview on pathways involved in the reduced apoptosis of RA-FLS and then discuss specially the possible roles of nitric oxide and the thioredoxin 1 redox system associated with apoptosis of RA-FLS.

Role of nitric oxide and vascular endothelial growth factor in fluoride-induced goitrogenesis in rats

Endemic fluorosis is a serious problem in public health. Previous studies have indicated that patients with thyroid goiters usually live in fluoride-affected areas. However, the mechanism of goitrogenesis caused independently by fluoride is still unclear. The principle objective of this study was to investigate the possible roles of nitric oxide (NO) and vascular endothelial growth factor (VEGF) in the genesis of fluoride-induced nodular goiters. Eighty SD rats (40 males and 40 females) at the age of 4 weeks were used to establish animal models via fluoride-supplemented drinking water. These rats were randomly divided into four groups of 20. Group 1 was used as the control and were given deionized water. Group 2 (LF), group 3 (MF), and group 4 (HF) were given deionized water containing 50mg/L, 100mg/L, and 200mg/L of sodium fluoride (NaF), respectively. Thyroid samples were collected on day 150. Pathological observation was performed to evaluate structural changes in the thyroid gland. The expression of VEGF mRNA in the thyroid glands was assessed by reverse transcriptional PCR. The serum NO level was analyzed by spectrometric methods. In addition, immunohistochemistry was conducted to evaluate expression and deposition of VEGF in the thyroid gland. The results showed that the average relative weight of the thyroid glands of rats in the fluoride-treated groups was significantly higher than that in control rats (p<0.05). The proliferation and dilatation of capillary blood vessels, enlarged follicles with excessive colloid, and obvious nodules were found in the thyroid glands of fluoride-treated rats. Compared to the control group, the expression of VEGF mRNA in the thyroid gland and the serum NO levels in the fluoride-treated groups were significantly increased (p<0.05). Furthermore, the deposition of VEGF in epithelial and follicular cells of the thyroid gland was significantly higher in fluoride-treated groups than in the control group. These results suggested that abnormal expression of VEGF induced by fluoride can lead to the proliferation of vascular endothelial cells in the thyroid gland. Accordingly, VEGF oversecreted locally by vascular endothelial cells might contribute to the proliferation of epithelial and follicular cells, resulting in the formation of hyperplastic nodules and enlargement of the thyroid gland. Furthermore, we proposed that there might be a positive feedback mechanism between NO and VEGF expression in fluoride-induced goiter formation. It was concluded that angiogenic and vasodilative factors such as VEGF and NO must be involved in fluoride-induced thyroid goitrogenesis.

Kidney is in Trouble with Mediators

The kidneys receive 20-25 % of cardiac output and play a main role in the control of cardiovascular homeostasis. It is an endocrine organ that regulates and produces many substances, scavenger particles and immune complexes. Cytokines, growth factors, reactive oxygen metabolites, bioactive lipids, proteases, vasoactive substances such as nitric oxide (NO), adrenomedullin (AM), urotensin-II (U-II), have been released in several diseases, and kidney is one of mostly affected organs in body. Some of these mediators act in a paracrine fashion while some act in autocrine. They play important roles in modulating the cardiovascular responses, renal hemodynamics, and probably in mediating the clinical and laboratory manifestations of several renal diseases. These mediators are like "a double edged sword". While small amounts of them mediate many physiological events, little excess may cause the damage to the healthy cells. Many investigators have searched the role(s) of mediators in several diseases. However, the findings are mostly like the model of "chicken and egg", and indistinguishable as to whether they are the causes of, or results of the diseases. We will discuss mainly the possible roles of NO, AM and U-II in children with several renal diseases and summarize what is known, and what must be known about these mediators.

Nitric Oxide and Luteal Blood Flow in the Luteolytic Cascade in the Cow

The corpus luteum (CL) of the estrous cycle in the cow is a dynamic organ which has a lifespan of approximately 17-18 days. The main function of the CL is to produce progesterone (P) that requires for achievement and maintenance of pregnancy. If pregnancy does not occur successfully, the CL must regress within a few days to induce the next chance of ovulation. As the CL matures, the steroidogenic cells establish contact with many capillary vessels, consequently the CL is composed of a large number of vascular endothelial cells that can account for up to 50% of all cells. Therefore, blood vessels and blood flow within the CL have an essential role in luteal function. Nitric oxide (NO), a strong vasorelaxant, is now known to play key roles in a variety of physiological process. Indeed, NO has established itself as a polyvalent molecule which plays a decisive role in regulating multiple functions within female reproductive system. In the CL, NO is produced and regulates luteal blood flow, P secretion and apoptosis of luteal cells as well as endothelial cells. This review describes the current investigation for possible roles of NO in the luteolytic cascade within the bovine CL.

Downregulative Effects of Nitric Oxide on Oocyte Fertilization and Embryo Development: Possible Roles of Nitric Oxide in the Pathogenesis of Endometriosis-associated Infertility

Aims: To investigate the effects of elevated nitric oxide (NO) levels in peritoneal fluids (PF) on oocyte fertilization and pre-implantation embryo development, and the relation of those effects to endometriosis-associated infertility. Methods: PF from women undergoing laparoscopy for infertility of minor endometriosis, tubal blockage and operation for tubal ligation was aspired at the pouch of the cul-de-sac during surgery. Oocytes and embryos of adult ICR mice were cultured in vitro with or without endometriotic PF. The fertilization rate of oocyte and the cleavage rate of 2-cell embryos were examined. Also, the clinical indexes of IVF-ET of women with minor endometriosis and tubal infertility were analyzed. Results: Oocyte fertilization rate of endometriotic women with IVF-ET treatment was significantly lower than that of tubal block women. The dose-related adverse effects of endometriotic PF and SNP (NO donor) in culture medium on oocyte fertilization and embryos development were confirmed. Conclusion: Increased NO levels in PF play an important role in mediating the effects of endometriotic PF on oocyte fertilization and embryo development. IVF might serve as an alternative treatment for endometriosis-associated infertility.

Production, localisation and possible roles of nitric oxide in drought-stressed grapevines

Background and Aims: The aim of this study was to monitor nitric oxide (NO) production in response to progressive soil drying as well as to evaluate its possible role as an intermolecular signalling molecule mediating drought-stress responses in grapevines. Methods and Results: NO production in response to water stress was examined in potted grapevine plants (Vitis vinifera L. cv. Mavrodafni). The cellular sites of NO production and localisation in stressed plants were monitored by fluorometric techniques. Results indicated that both abscisic acid and NO concentrations increased significantly in leaves of stressed plants. The stomatal guard cells seemed to be the sites of earlier NO accumulation. The changes in stomatal conductance seemed to be closely related to both abscisic acid and NO increase, while there was no significant correlation between stomatal conductance and hydrogen peroxide concentration. Conclusions: The close relationships between stomatal conductance and NO concentrations indicate a potential role of this molecule in drought-signalling pathway in grapevines. Significance of the Study: Results suggest a contribution of hydrogen peroxide to triggering NO production as well as a possible role of NO on both stomatal closure and antioxidant defence in drought-stressed grapevines.

Nitric oxide in bovine corpus luteum: Possible mechanisms of action in luteolysis

ABSTRACTAlthough prostaglandin (PG) F2α is considered as the principal luteolytic factor, its action on the bovine corpus luteum (CL) is mediated by other intraovarian factors. Among them, nitric oxide (NO) seems to play a mandatory role in luteolysis. In this article we review the background and current status of work on possible roles of NO in the CL function, based on available information and our own experimental data. NO is produced in all three main types of bovine CL cells: steroidogenic, endothelial and immune cells. PGF2α and some luteolytic cytokines (tumor necrosis factor, interferon) increase NO production and stimulate NO synthase expression in the bovine CL. NO inhibits progesterone production, stimulates the secretion of PGF2α and leukotriene C4, reduces the number of viable luteal cells and, finally, participates in functional luteolysis. NO induces the apoptotic death of CL cells by the modulation of bcl‐2 family gene expression and the stimulation of caspase‐3 gene expression and activity. However, this simple molecule shows both luteolytic and luteotropic actions during the estrous cycle in ruminants. The aim of this overview is to present and discuss the recent findings crucial for understanding NO role in the process of CL regression in cattle.

Higher serum nitrate levels are associated with poor survival in lung cancer patients

Objectives: Angiogenic factors induce tumour growth and angiogenesis which leads to tumour metastasis and a poor survival rate. This study aimed to assess the possible roles of nitric oxide (NO) and vascular endothelial growth factor-A (VEGF-A) in the overall survival of patients with late stage lung cancer. Design and Methods: The study was carried out with primary lung carcinoma patients ( n = 31) and healthy controls ( n = 15). Pre- and post-cisplatin-based chemotherapy serum nitrite/nitrate levels were measured as nitrite after enzymatic conversion followed by Griess reaction and serum VEGF-A analysis was performed using ELISA. After patient follow-up, survival rates were calculated by using the Kaplan–Meier method [Dudek et al. Cancer Invest 2005; 23(3):193–200]. Results: The serum nitrite/nitrate and VEGF-A levels of lung cancer patients and the control group were 93.7 ± 48.9 and 63.7 ± 32.2 μM ( p = 0.018), and 620 ± 491 and 255 ± 157 pg/mL ( p = 0.001), respectively. High nitrite/nitrate (> 67.2 μM) concentration had statistically significant effects on overall survival (Cox analysis, p = 0.026). The overall survival of the lung cancer patients with higher serum nitrate concentrations was significantly less than the ones with lower serum nitrite/nitrate (Kaplan–Meier survival functions test, log rank significance = 0.0007). Conclusion: Our results suggest that having a high serum nitrite/nitrate concentration is a strong indicator of poor survival for late stage lung cancer patients. However, this conclusion deserves to be elucidated further by using a larger sample size.

Formation and possible roles of nitric oxide in plant roots

Nitric oxide has been reported to act as a signalling molecule in different plant tissues and to participate in a variety of physiological processes. It is produced by different enzymes and sources. The root-specific plasma membrane-bound enzymes forming NO from the substrates nitrate and nitrite are of particular interest because roots serve as interfaces between plants and the soil. The co-ordinated activity of the root-specific plasma membrane-bound nitrate reductase (PM-NR) and nitrite:NO reductase (NI-NOR) suggests that NO might also be involved in root signalling and development. The rate of enzymatic production of this NO depends largely on the environmental conditions, mainly the availability of nitrate and oxygen and it is proposed that this NO plays a role during anoxia as an indicator of the external nitrate availability and in regulating symbiotic interactions at the root surface.

Elevated serum nitric oxide metabolites in biliary atresia

Biliary atresia (BA) remains one of the most intractable liver diseases in children. The aim of this study was to investigate the possible roles of nitric oxide (NO) in BA. Serum levels of nitrite and nitrate (NO production) were determined using a colorimetric method from 65 post-operative BA patients and 12 healthy children. The patients were categorized into two groups according to their jaundice status, and serum alanine aminotransferase (ALT, a marker for liver injury). Unpaired t tests were used. Data are expressed as mean and SD in terms of mumol/l. Age and gender between BA patients and controls were comparable. Serum NO metabolites of BA patients was higher than the controls (79.77+/-21.22 vs. 65.75+/-9.44, P=0.001). Subgroup analysis revealed that there was no difference in serum nitrate/nitrite levels of BA patients without jaundice compared to those with jaundice (78.85+/-23.23 vs. 80.90+/-18.76, P=0.70). However, patients with serum ALT> or =100 IU/l had higher levels of serum NO metabolites compared to those with serum ALT<100 IU/l. In conclusion, NO production was elevated in BA patients compared to normal controls. Serum NO was associated with serum ALT levels, but not with jaundice status, in BA patients. These suggest that NO plays a role in the pathophysiology of liver injury in post-operative BA.

Possible roles of nitric oxide in the adhesion of glioma cells to extracellular matrix components after ionizing irradiation

Possible roles of nitric oxide in the adhesion of glioma cells to extracellular matrix components after ionizing irradiation

GEA 3162 decomposes to co-generate nitric oxide and superoxide and induces apoptosis in human neutrophils via a peroxynitrite-dependent mechanism.

1. GEA 3162 (1,2,3,4,-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl)-chloride), has powerful effects on neutrophil function and apoptosis, but the underlying mechanisms are unclear, particularly with respect to the possible roles of nitric oxide (NO) and/or peroxynitrite (ONOO(-)). 2. Our hypothesis was that GEA 3162 is a generator of ONOO(-) and that its biological effects on neutrophil apoptosis differ from those of a conventional NO donor. The effects of GEA 3162 were compared to those of the established ONOO(-) donor, 3-morpholinosydnonimine (SIN-1), and the NO donor, diethylamine diazeniumdiolate (DEA/NO) in neutrophils from healthy volunteers. Electrochemical detection and electron paramagnetic resonance were used to define the NO-related species generated from these agents. 3. GEA 3162 and SIN-1 influence neutrophil apoptosis differently from DEA/NO. All three compounds induced morphological neutrophil apoptosis. However, both GEA 3162 and SIN-1 paradoxically inhibited internucleosomal DNA fragmentation, whereas DEA/NO induced fragmentation compared to control. 4. In contrast to DEA/NO, generation of free NO was not detectable in solutions of GEA 3162 or SIN-1 (100 microm). However, Cu/Zn superoxide dismutase (SOD; 50-750 U ml(-1)) unmasked NO generated from these compounds in a concentration-dependent manner. GEA 3162 and SIN-1 oxidised the O(2)(-)- and ONOO(-)-sensitive dye, dihydrorhodamine 123 (DHR 123; 1 microm), suggesting that ONOO(-) released from these compounds is responsible for oxidation of DHR 123. 5. We conclude that GEA 3162 is an ONOO(-) donor with pro-apoptotic properties that more closely resemble SIN-1 than the NO donor, DEA/NO. Moreover, unlike NO, ONOO(-) induces apoptosis in neutrophils via a mechanism that does not require DNA fragmentation.

Possible roles of nitric oxide in the adhesion of glioma cells to extracellular matrix components after ionizing irradiation

Nitric oxide (NO) is a stable free radical in tumors and normal tissue. The generation of free radicals by irradiation may play a role in the reoxygenation of tumor and in the emergence of late toxicity of normal tissue by the interaction with nitric oxide as well as in the tumor progression and metastasis. In this study, we investigated the effect of NO on the adhesion capacity of glioma cells to extracellular matrix components after exposed to γ-irradiation. Three isoforms of NO synthases (NOS) were determined in cells using immunohistochemical staining. The NOS enzymatic activity was measured by determination of NO products using either C14-citrulline measurement or Griess reaction assay. The C6 glioma cells were pretreated with either SNAP, which is an NO donor, or L-NNA, which is an NO synthase inhibitor, followed by irradiation with a total dose of 200, 400 and 800 cGy at a dose rate of 90 cGy/min using Ce-137 irradiator. The adhesion assay was performed in vitro with extracellular matric components including fibronectin, laminin I and collagen IV respectively. Our results showed that 1) The g-irradiation can enhance the endogenous NO production in glioma cells. The enhancement of NO productivity was further achieved to about 3 folds in LPS and IFN-g treated cells indicating the promotion of NO production by ionizing irradiation in glioma cells. 2) At the irradiation dose of 400 and 800 cGy, the inhibition of glioma cell adhesion to ECM by exogenous NO was reduced. Meanwhile, the enhancement of adhesion of glioma cells exposed to irradiation and treated with L-NNA was also abolished in compared to the cells without irradiation. 3) Surviving fraction study for the NO-treated cells under irradiation indicated that 400 cGy is critical for NO-related adhesion since the exogenous NO could decrease surviving fraction to about 50% while inhibition of NO synthase enzyme activity by L-NNA could increase of surviving fraction to about 23%. Our results indicated that ionizing irradiation has an impact on the adhesion of glioma cells and the free radical nitric oxide may have a role as one of the mediators during the tumor metastasis

Ghrelin protects against ethanol-induced gastric ulcers in rats: studies on the mechanisms of action.

Ghrelin, the endogenous ligand for GH secretagogue receptors, has been reported to influence acid gastric secretion and motility, but its potential gastroprotective effect is unknown. The aims of this study were 1) to examine the effects of central and peripheral administration of ghrelin on ethanol-induced gastric ulcers in conscious rats, and 2) to investigate the possible roles of nitric oxide (NO), vagal nerve, and sensory fibers in the gastric effects of ghrelin. Ghrelin was administered either intracerebroventricularly or sc 30 min before ethanol, and mucosal lesions were examined macroscopically. Additionally, rats were either treated with the inhibitor of NO synthesis N(omega)-nitro-L-arginine methyl ester (L-NAME) or underwent bilateral cervical vagotomy or capsaicin-induced sensory denervation. Conventional histology and immunohistochemistry for ghrelin, gastrin, and somatostatin were performed on gastric specimens from representative rats. Central ghrelin (4-4,000 ng/rat) dose-dependently reduced ethanol-induced gastric ulcers by 39-77%. Subcutaneous ghrelin administration (80 micro g/kg) reduced ulcer depth only. L-NAME and capsaicin, but not vagotomy, prevented the gastroprotective effect of central ghrelin (4000 ng/rat). This is the first evidence that ghrelin exerts a potent central gastroprotective activity against ethanol-induced lesions. The gastroprotective effect of ghrelin is mediated by endogenous NO release and requires the integrity of sensory nerve fibers.

Possible roles of nitric oxide in the physiology and pathophysiology of the mammalian cochlea.

Nitric oxide (NO) has been implicated as a mediator of vasodilation and neurotransmission in the mammalian cochlea. This is demonstrated by the presence of nitric oxide synthase (NOS) and nitric oxide (NO) in the blood vessels and the organ of Corti in the cochlea. It is not certain if the neurons in the spiral ganglion produce NO since no fluorescent signal could be detected by 4,5-diaminofluorescein diacetate (DAF-2DA), a fluorescent indicator of NO. To determine if NO/peroxynitrite plays any role in neurodestruction observed in ischemic cochlea of the guinea pig, the effects of NO donors, such as S-nitrosocysteine (S-NC) and nitroglycerine (NTG); peroxynitrite generators, such as 3-morpholinosydnonimine (SIN-1); peroxynitrite inhibitors, such as superoxide dismutase plus catalase (SOD/Cat); and NOS inhibitors, such as N(G)-nitro-L-arginine methyl ether (L-NAME) were tested on normal and ischemic cochleae. The level of NO in the cochlea after 20 to 120 minutes of ischemia was indicated by measurement of nitrites/nitrates in the perilymph. The evidence gathered from these experiments indicates that NO or peroxynitrite is not necessarily destructive to auditory hair cells, and in fact, exogenous NO may protect neural structures in the cochlea from damage under ischemic conditions.