Septic shock down-regulates L -arginine /NOS /NO pathway of platelet and aortic intima in rats

AIM: To investigate alteration and cross link of the aortic and platelet endogenous L -arginine/NOS/NO pathway induced by septic shock.METHODS: The septic shock model was made in rats by caecal ligation and puncture. NO^-₂/NO^-₃ production released from aortic and platelet was measured with Greiss assay. NOS activity and L-arginine transport activity were detected by isotope tracer method. RESULTS: Both in early and late stage of septic shock, NO^-₂/NO^-₃ production, NOS activity, and the L-arginine transport from the aorta intima and platelets were obviously decreased, while those of the aorta media and adventitia were obviously increased (P<0.01), but high-affinity L-arginine transport activity from the aorta intima and platelets was increased in early stage of septic shock (P>0.05 and P<0.05), as compared with the sham group, respectively. The inhibitory effects of NO^-₂/NO^-₃, NOS activity and the L-arginine transport showed a positive correlation between platelet and aortic intima (P<0.01). CONCLUSION: Septic shock down-regulates endogenous L-arginine/NOS/NO pathway in aortic intima and platelet, up-regulates L-arginine/NOS/NO pathway of aortic media and adventitia. Detection of the alteration of endogenous L-arginine/NOS/NO pathway in platelet might act as an indirect method to assess the endothelial dysfunction involving the pathogensis of septic shock.     

Changes of L-arginine,NOS/NO pathway in adventitia of rats with sepsis

AIM: In this study, we aimed to explore the alteration and pathophysiological significance of the L-arginine (L-Arg)/NOS/NO pathway in the adventitia of rats with sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP). Rat cardiac function was determined. NO generation, NOS activity and L-Arg transport were measured. The iNOS mRNA levels was determined by using RT-PCR. RESULTS: Cecal ligation and puncture induced severe sepsis with severe low glucose, high lacticemia and cardiac function inhibition. The iNOS activity was increased by 2.8-fold compared with controls (P<0.01) and the iNOS mRNA level was elevated-6-fold (P<0.01). The NO level in plasma and incubation media (incubation for 40 min) in the sepsis group was increased by 144% and 273% (both P<0.01), respectively. CONCLUSION: The results demonstrated that the L-Arg,NOS/NO pathway was activated in vascular adventitia of rats with sepsis shock. The aortic adventitia L-Arg/NOS/NO pathway might play an important role in the pathogenesis of sepsis and septic shock.     

Changes of nitric oxide synthase and nitric oxide in lung of smoking rats

AIM:To observe the changes of iNOS and eNOS in lung tissue and NO in bronchoalveolar lavage fluid (BALF) in smoking rats.METHODS:80 Wistar rats were divided into control, smoking group, L-NIL group and L-NAME group (rats were exposed to smoke and injected (i.p.) with selective iNOS inhibitor L-NIL or NOS inhibitor L-NAME). iNOS and eNOS protein levels in whole lung were detected by immunohistochemical staining, and NOS mRNA was quantified using RT-PCR. In addition, NO₂^-/NO₃^- was determined using Griess assay.RESULTS:The expression of iNOS mRNA and protein in smoking rats increased, the expression of eNOS mRNA and eNOS protein decreased, and the total cell count and the level of NO₂^-/NO₃^-in BALF increased(P＜0.05). In vivo, L-NIL reduced the total cell count and NO₂^-/NO₃^- in BALF (P＜0.05), while L-NAME had no effect on them.CONCLUSION:Cigarette smoke increased expression of iNOS mRNA and protein and decreased expression of eNOS mRNA and protein. The large amount of NO generated by iNOS may amplify inflammation in lung tissue.     

The kinetic alteration of nitric oxide formation in the lungs in the development of pulmonary fibrosis of rats

AIM: To observe the kinetic alteration of nitric oxide formation in the lungs in the development of pulmonary fibrosis in the rat. METHODS: The contents of hydroxyproline in the lungs, NO₂^-/NO₃^- (nitrite/nitrate) in out-flowing and in-flowing pulmonary blood (OPB, IPB) were assayed on the day 7, 14, 21, 30 and 70 after intratracheal administration of bleomycin A₅ . The content of NO₂^-/NO₃^- in supernatants of culture of the alveolar macrophages (AMs) and the amount of iNOS positive stain cells in lung tissue section were also observed in the rat on 14th day after-bleomycin A₅ administration. RESULTS: The content of lung hydroxyproline had no change on the 7th day, increased on the 14th day (P＜0.05), increased significantly on the 21th day, 30th day and 70th day post-bleomycin A₅ compared with control rats. On the 7th day and 14th day, the content of NO^- ₂ /NO₃^- increased in OPB and decreased in IPB (P＜0.01). On the 21th day, the content of NO₂^-/NO₃^- abated in OPB (P＞0.05) but still decreased in IPB (P＜0.01). On the 30th day and the 70th day, the NO₂^-/NO₃^- level recovered both in OPB and IPB. AMs from rats on the 14th day post-bleomycin A₅ showed significant elevation (P＜0.01) in NO₂^-/NO₃^- level. The amount of iNOS positive stain cells increased in rats on the 14th day post-bleomycin A₅. CONCLUSION: The amount of NO in the lungs was high in the initial phase of fibroproliferative reaction induced by bleomycin A₅ ,and these might be associated with the enhanced ability of AMs to release NO and the increased amount of iNOS.     

Effect of taurine on L-arginine/NO pathway in erythrocytes of rats of hypertension with insulin resistance induced by fructose

AIM and METHODS:The present study observed the change of L-arginine(L-Arg)/Nitric oxide(NO)pathway in ergthrocytes in hypertension with insulin resistance rat induced by fructose and the effect of taurine on L-Arg/NO pathway.RESULTS:Drinking 4%fructose, while inducing blood pressure, glucose and plasma insulin contents increase, obviously decreased the maximal velocity of L-Arg transport about 31%and 37%(P<0.01), more than that of control group in total and Y⁺ carrier, the NO synthase(NOS)activity, nitrite(NO₂^-)content and cyclic guanylate monophosphate(cGMP)level more than that of control group, but obviously enhanced Michaelis Constant(Km)about 35%and 30%(P<0.01)more than that of control group in total and Y⁺ carrier transport.The taurine treatment significantly counteracted the above changes.CONCLUSION:There exists a functional disturbance in L-Arg/NO system in the erythrocyte of hypertension rats with insulin resistance, but taurine can obviously enhanced the maximal velocity of L-Arg transport and NOS activity.Thus, it appears that taurinemay have vital value in the treatment of hypertension with insulin resistance.     

Detection of serum MDA,NO and INOS in patients with SARS andits clinical significance

AIM: To observe free radicals (MDA, NO) and iNOS of patients with severe acute respiratory syndrome (SARS) and to explore its significance. METHODS: MDA, NO₂^-/NO₃^- and iNOS were determined in SARS patients during the early, recovery and follow-up stage, front doctors and nurses (contact group) and health people (health control). RESULTS: The level of MDA during first stage was higher than that of recovery stage and the MDA level of recovery stage was higher than that of follow-up stage, contact group, and health control group (P<0.01). The content of NO₂^-/NO₃^- during early stage was higher than that of other groups, and the NO₂^-/NO₃^- contents of recovery stage, follow-up stage were higher than that of contact group and health control group (P<0.01), respectively. The mean of iNOS during early stage was highest than that of other stages (P<0.01) and the mean of recovery stage was higher than that of contact group (P<0.05), there were no difference in iNOS activity among any other groups (P>0.05). CONCLUSION: The pathological injury in pathogenesis of SARS is related to free radicals.     

Phenytoin inhibited changes in nitric oxide of rat hippocampus induced by stress

AIM: To investigate the changes in nNOS and iNOS expression of hippocampal CA3 pyramidal neurons and NO₂^-/NO₃^- level of hippocampal homogenate of rats induced by stress, and to explore the effect of phenytoin on them. METHODS: Rats were subjected to forced-swimming stress, phenytoin was administered(ip) at 30 min before stress. Using the immunohistochemistry and the computerized image technique, the expression levels of nNOS and iNOS of rat hippocampal CA3 pyramidal neurons were assayed quantitatively, and the NO₂^-/NO₃^- level of hippocampal homogenate was also measured using nitric acid deoxidize enzyme method. RESULTS: The nNOS average grey degree of hippocampal CA3 pyramidal neurons was significantly lower in stress group (155.42±3.77)than that in control group(164.54±4.62)and in stress plus phenytoin group(164.27±2.55)(P<0.01); The iNOS relative sectional area proportion of hippocampal CA3 pyramidal neuron was significantly larger in stress group(5.87%±2.90%) than that in control group (0.90％±0.89%) and in strers plus phenytoin groups (0.90%±0.88%)(P<0.01); The NO₂^-/NO₃^- level of hippocampal homogenate was significantly higher in stress group(42.75 umol/L±14.49 umol/L)than that in control group(21.23 umol/L±6.99 umol/L)and in stress plus phenytoin group(18.40 umol/L±8.11 umol/L)(P<0.01). CONCLUSION: It is suggested that the stress could induce nNOS and iNOS expression in CA3 pyramidal neurons and excessive production of NO in hippocampus of rats, which could be inhibited by phenytoin.     

Effect of antiserum against complement C5b-9 complexes on nitric oxide(NO) synthesis and pathologic changes in renal tissue of ATSN rats

AIM: To explore the effect of antiserum against rat complement C5b-9 complexes on nitric oxide synthesis and pathologic changes in renal tissue of rats with mesangioproliferative glomerulonephritis. METHEDS: The rat model of mesangioproliferative glomerulonephritis,namely,anti-thymocyte serum nephritis(ATSN) was established and the rats with ATSN were treated with antiserum against complement C5b-9 complexes. Some parameters related to NO and pathologic changes of the rats were observed.RESULTS: Anti-C5b-9 serum not only reduced the expression of inducible NO synthase(iNOS) mRNA in renal tissue and urinary content of nitrate/nitrite(NO₃^-/ NO₂^-) of rats with ATSN, but also reduced renal pathologic changes. L-N G-nitro arginine methylester (L-NAME) also reduced the contents of urinary NO₃^-/NO₂^- and the renal pathologic changes of rats with ATSN. CONCLUSION: The antiserum against rat complement C5b-9 complexes inhibited glomerular NO synthesis and glomerular mesangial cell proliferation of rats with ATSN.     

Effect of nitric oxide and peroxynitrite on lung injury induced by ischemia-reperfusion of hind limbs in rats

AIM:To observe the changes in nitric oxide(NO) and peroxynitrite anion (ONOO^- ) in the injuried lung following the ischemia-reperfusion of hind limbs and evaluate the contribution of NO and ONOO^- to tissue injury.METHODS:A model of hind limbs ischemia was made by clamping infrarenal aorta with a microvascular clip and lung injury occurring after reperfusion.Lung t issue was obtained from the animals received sham operation(group 1),4 hours ischemia without reperfusion(group2),1 hour reperfusion following 4 hours ischemia(group3)and 4 hours reperfusion fol owing 4 hours ischemia(group4).The contents of MDA,NO₂^-/NO₃^- and the activities of SOD in the lung were examined.Immunohistochemical echnique was used to determine the immunoreactivity to iNOS and nitrotyrosine(NT)-a specific "footprint" of peroxynitrite.RESULTS:Compared with group1 and group2,the contents of MDA and NO₂^-/NO₃^- increased significantly (P<0.05) and the activities of SOD decreased markedly(P＜0.05) in group3 and group4.Immunohistochemical examination demonstrated intense staining for iNOS and NT throughout the lung in group3 and group4.CONCLUSION:NO and ONOO^- are involved in oxidant-mediated lung injury following reperfusion of ischemic hind limbs.     

Protective effect of Ginkgo biloba extract on testicular tissue of diabetic rats

AIM: To investigate the protective effect of Ginkgo biloba extract (GBE) on diabetic testis and explore its possible mechanism. METHODS: Testicular structure of streptozotocin-induced diabetic rats was observed under light microscopy (LM) and transmission electron microscopy (TEM). Content of malondialdehyde (MDA), NO₂^-/NO₃^- and activity of superoxide dismutase (SOD), nitric oxide synthase (NOS) were determined in testicular homogenate. RESULTS: In diabetic rats, it was manifestated as deformation of seminiferous tubule, atrophy and shedding of germinal epithelium under LM, while expansion of smooth endoplasmic reticulum, formation of fatty vacuoles and decrease of lysosome obviously in the cytoplasm of sertoli cell under TEM, the injury of testicular tissue was improved by GBE. Compared with diabetic rats, activity of SOD increased while activity of tNOS and iNOS, content of MDA and NO₂^-/NO₃^- decreased in GBE-treated rats. CONCLUSION: GBE could effectively prevent the development of diabetic testis and the effect may be partly achieved by resisting lipid peroxidation,restraining the activity of testicular tissue iNOS and reducing the pathological alterations of NO.     

The renal L-arginine/nitric oxide pathway and erythrocyte L-arginine transport in spontaneously hypertensive rats

AIM: To investigate the changes of the renal L-arginine /nitric oxide pathway and the relationship of L-arginine transport between kidney and erythrocytes in spontaneously hypertensive rat (SHR). METHODS: Sixteen week old SHR, 16 week old SHR with captopril (CAP) treated for four weeks and 16 week old WKY rats were used in the experiment. L-arginine transport, NO synthase(NOS) activity, nitrite and cyclic GMP (cGMP) content were measured in renal tissue or erythrocytes. RESULTS: In the renal tissue, compared with that of WKY group, the Vmax of high-or low-affinity L-arginine transporter, NOS activity, NO₂^- and cGMP content of SHR group were significantly decreased (P＜0.01 or P＜0.05). The Vmax of high-affinity L-arginine transporter and NOS activity of CAP group were significantly enhanced as compared with SHR group (+90%, P＜0.01; +58.6%, P＜0.05). The NOS activity had significant positive correlation with the Vmax of high-affinity L-arginine transporter (r=0.585, P＜0.05). The changes of erythrocyte L-arginine transport were the same as that of kidney. The Vmax of SHR group was lower than that of WKY group (-30%, P＜0.01), and the Vmax of CAP group was higher than that of SHR group (+26.5%, P＜0.01). Km was not significantly changed. There is a positive correlation between the Vmax of L-arginine transport in erythrocyte and the Vmax of high- or low-affinity L-arginine transporter in renal tissue, (r=0.8434, P＜0.01, high-affinity; r=0.5255, P＜0.05, low-affinity). CONCLUSION: There existed a functional inhibition in L-arginine/nitric oxide pathway in the kidney of SHR. It can be recovered obviously by captopril treatment. The changes of L-arginine transport in kidney coincide with that in erythrocyte.     

The protection of the hepatic ischemic preconditioning is concerned with the NO/ET-1 system

AIM: To study the relationship between the disturbance of nitric oxide/endothelin-1(NO/ET-1) and hepatic ischemia/reperfusion(I/R) injury as well as the regulation of NO/ET-1 system by hepatic ischemic preconditioning(IPC). METHODS: The changes of NO/ET-1 system and their relationship with hepatic I/R injury were compared between I/R group and IPC+I/R group in a rat hepatic I/R model. Two hours after reperfusion, the liver tissues were detected by RT-PCR to see whether there was inducible nitric oxide synthase (iNOS) mRNA expression. RESULTS:In the acute phase of hepatic reperfusion, the ratio of NO/ET-1 was reduced, which was due to a significant reduction of NO₂^-/NO₃^- (the metabolic product of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and of MDA in liver tissue were increased but ATP in liver tissue was reduced, the hepatic damage was deteriorated. The protection of the hepatic IPC was concerned with the elevation of the ratio of NO/ET-1 caused by the elevation of NO₂^-/NO₃^-, and reduction of ET-1 as well. There was no iNOS mRNA detected in the liver tissues.CONCLUSION: Hepatic I/R injury is related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be conducted by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this situation.     

Protective effects of extract of Ginkgo biloba on diaphragm of diabetic rats

AIM: To investigate the effects of extract of Ginkgo biloba (EGb) on diaphragm from diabetic rats. METHODS: Sprague-Dauley rats were divided into three groups: normal control, diabetic group and EGb treatment group. The morphologic changes of diaphragm tissues were studied by light and electron microscopy, the activities of succinate dehydrogenase (SDH), superoxide dismutase (SOD), nitric oxide synthase (NOS) and contents of malondialdehyde (MDA), nitric oxide (NO₂^-/NO₃-) in the diaphragm mitochondria were assayed by spectophotometer, respectively. RESULTS: The activities of SOD, SDH decreased in diabetic diaphragm mitochondria, but the activitiy of NOS, the contents of NO₂^-/NO₃^-, MDA increased compared with control group. The activities of SOD, SDH were increased as well as NOS were decreased and the contents of NO₂^-/NO₃^-, MDA decreased in EGb treatment group compared with the diabetic group. CONCLUSION: EGb may protects the diaphragm mitochondria of diabetic rats by enhancing the function of respiratory chain, anti-oxidation and decreasing NO level.     

Role of endogenous nitric oxide in apoptosis of alveolar epithelial cells in the development of pulmonary fibrosis in rats

AIM: To study the role of high level of endogenous nitric oxide (NO) in apoptosis of alveolar epithelial cells in the development of pulmonary fibrosis in rats. METHODS: The content of nitrite/nitrate (NO₂^-/NO₃^-) in out-flowing pulmonary blood (OPB) was assayed by nitric acid reduction method. The apoptosis of alveolar epithelial cells was observed by TdT-mediated dUTP nick-end labeling (TUNEL) and electron microscopy, respectively. The above indices were observed on the day 14 and the day 30 after intratracheal administration of BLMA₅ alone or along with blockade of iNOS by aminoguanidine (AG) in rats. RESULTS: (1) Both the content of NO₂^-/NO₃^- in OPB and the number of apoptotic alveolar epithelial cells in lung were increased in BLMA₅ 14 d group, compared with normal control group and BLMA₅ 30 d group, respectively (P<0.05). The high level of NO₂^-/NO₃^- in OPB and the apoptosis of alveolar epithelial cells were ameliorated by AG. CONCLUSION: The apoptosis of alveolar epithelial cell is induced by high level of endogenous NO in the development of pulmonary fibrosis.     

The augmentative effect of inducible nitric oxide synthase on pulmonary fibrosis progression

AIM: To study the up-regulation of inducible nitric oxide synthase (iNOS) in lung of pulmonary fibrosis and its relationship with fibrosis. METHODS: The changes of amount of iNOS positive stain cells and type Ⅰ?Ⅲ collagen were examined on the day 7, 14 and 30 after intratracheal administration of bleomycin A₅. The contents of NO₂^-/NO₃^- (nitrite/nitrate) in out-flowing pulmonary blood (OPB), hydroxyproline in lung and the histological changes were detected after iNOS was blocked by aminoguanidine (AG). RESULTS: (1) The number of iNOS-positive stain cells increased significantly in BLMA₅ 7 d, 14 d and 30 d groups compared with that in control group (P<0.01). Furthermore, the increment of the number of iNOS-positive stain cells in BLMA₅ 7 d, 14 d groups was more than that in BLMA₅ 30 d group. There was an increment of collagen in BLMA₅ 14 d group and in BLMA₅ 30 d group , with an increase in type Ⅲ collagen in BLMA₅ 14 d group and an increase in type Ⅰcollagen in BLMA₅ 30 d group. (2) The high level of NO₂^-/NO₃^- in OPB and hydroxyproline level in lung could be reversed by AG, a selective inhibitor of iNOS. Large amount of fibroblasts and macrophages were also abated by AG. CONCLUSION: In the development of pulmonary fibrosis, the expression of iNOS is up-regulated, which induces nitric oxide (NO) production and promotes propagation of pulmonary fibrosis.     

Effects of nitric oxide on hepatic encephalopathy in cirrhotic rats induced by LPS

AIM: To investigate the effects of nitric oxide (NO) on hepatic encephalopathy in cirrhotic rats induced by LPS. METHODS: The cirrhotic model of rats was established by complex pathogeny. Since the end of the 8 th week, the rats were intragastrically-infused with 0.9% salt, L-arginine(L-arg) and LNNA respectively for 2 weeks.The hepatic encephalopathy in cirrhotic rats were induced by 3 mg/kg LPS (ip) 4 hours before the rats were sacrificed. RESULTS: The normal behaviors and electroencephalograph were appeared in L-arg group. LNNA group showed hepatic encephalopathy. The content of NO₂^-/NO₃^- of brain tissue was markedly higher in L-arg group than LNNA group(P<0.05), but the content of histamine in brain tissue was lower in L-arg group than LNNA group(P<0.05). There was a negative correlation between the content of histamine in brain tissue and the content of NO₂^-/NO₃^- of brain tissue. CONCLUSION: NO can prevent hepatic encephalopathy in cirrhotic rats induced by LPS.     

Effects of nitric oxide on mitochondrial damage caused by exogenous calcium

AIM: To study the effects of nitric oxide (NO) on mitochondrial damage caused by exogenous calcium. METHODS: Normal myocardial mitochondria were divided into three groups; L-arginine control group (CG), Ca^2＋-damaged group (DG) and L-NAME-preserved group (PG). Mitochondria of all groups were incubated at 30 ℃ with reaction medium containing 20 μmol/L EDTA, 100 μmol/L CaCl₂ and 1 μmol/L L-NAME with 100 μmol/L CaCl₂ respectively. Then the NO₂^-/NO₃^- contents, mitochondrial viability and membrane potential were investigated. RESULTS: The NO₂^-/NO₃^- contents of DG was obviously higher than that of CG and PG, meanwhile, there was no obvious difference between CG and PG. Mitochondrial viability and membrane potential of DG were significantly lower than that of CG and PG, and negatively related to NO^-₂/NO^-₃ contents (r=-0.5297, P＜0.01; r=-0.6041, P＜0.01). But, the mitochondrial viability and membrane potential of PG were still lower than that of CG. CONCLUSION: Exogenous calcium could activate mitochondrial nitric oxide synthase resulting in NO production and the latter play an important role in decreasing mitochondrial viability and membrane potential.     

Effect of nitric oxide in ocular inflammatory response after intraocular lens implantation

AIM: To investigate the effect of nitric oxide (NO) in ocular inflammation after intraocular lens implantation. METHODS: All New Zealand rabbits were divided randomly into three groups: 1. control group, 2. L-arginine (L-Arg) group, 3. N-nitro-L-arginine (L-NNA) group. Extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens implantation (IOL) were operated in all animals of each groups. The inflammatory response of all rabbit eyes, including cornea edema and anterior chamber exudation were investigated 1, 3, 7, 14, 30 days afteroperation. Meanwhile, aqueous humor was drawn for white blood cell (WBC) counting and classifying, as well as for NO₂^-/NO₃^- measurement. RESULTS:NO₂^-/NO₃^- contents, total WBC and anterior chamber exudation in aqueous humor of L-Arg group were higher than that in control group. While that of L-NNA group were lower than that in control group.CONCLUSION:NO plays a role in intraocular inflammatory response after intraocular lens implantation. L-NNA, a nitric oxide synthase exhibitor, decreased NO contents, therefore it may reduce intraocular inflammatory response after intraocular lens implantation.     

Effects of taurine-magnesium complex on vascular endothelium and hemorheology in rats in vivo

AIM: To study the protective effects of taurine-magnesium complex (TMC) on endothelium and hemorheology in rats. METHODS: A model of the endothelial damage was made by means of giving rats an injection of adrenaline and making them swim in ice-cold water, then number of circulating endothelial cells (CEC) in whole blood, plasma ET-1 and NO₂^-/NO₃^- content, NOS activity and rheology were determined, respectively. The protective effects of TMC were also observed. RESULTS: An increase in the number of CEC accompanied by abnormal whole blood viscosity, and endothelium-derived ET-1 were observed in model rats. Both the NO₂^-/NO₃^- content and NOS activity were declined significantly in model rats. TMC reduced the number of CEC, resumed NO₂^-/NO₃^- content and NOS activity, and improved the whole blood viscosity in a dose-dependent manner in model rats. CONCLUSION: Ice-cold water bath with adrenaline causes an acute damage of vascular endothelium and abnoramal rheology. TMC protects against the injury of vascular endothelium and improves the hemorheology.     

Study on changes of ET、NO level and tumor weight of mice bearing S180 model and their relationships

AIM: To approach the changes of ET and NO levels of mice bearing sarcoma 180 (S₁₈₀ ) during different period(5、10 and 15 days) and the relationship between ET、NO and tumor’s development METHODS: Adopting mice bearing S₁₈₀ as the models, the levels of ET and NO₂^-/NO₃^- in serum were detected, and the weight of isolated tumors was measured On the basis of the regulation of these changes, their relationships were explored RESULTS: The levels of ET and NO₂^-/NO₃^- of mice bearing S₁₈₀ were higher than that of the control group (not bearing tumor) ( P< 0.05) Along with the development of the tumors, the levels of NO₂^-/NO₃^-and tumors weight both increased ( P< 0 05) ET also had an increasing tendency There was a positive correlation between the level of NO₂^-/NO₃^- and tumor weight ( r =0.995, P< 0.05) Ratio value of (NO₂^-/NO₃^-)/ET decreased at first and then increased CONCLUSION: ET and NO have links with the development of S₁₈₀ There may be cooperation between ET and NO during the development of tumor.