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Einstein (Säo Paulo) ; 21: eAO0302, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1528572


ABSTRACT Objective: We hypothesized that perinatal manipulations of the nitrergic system would affect adult animal behaviors. Methods: We tested this hypothesis by perinatally administering N(G)-Nitro-L-arginine methyl ester (L-NAME), a non-specific antagonist of nitric oxide synthase for 15 days and assessed anxiety- and depression-like behaviors in adult mice. At 70 days of age, the mice were subjected to a battery of tests consisting of the open-field, light/dark box, forced swim, and tail-flick tests. The tests were performed at two-day intervals, and the order of the tests within the battery was determined according to the progressive invasiveness degree. Results: L-NAME-treated animals exhibited decreased anxiety-like behavior in the light/dark box and open field tests, with no change in locomotor activity. Additionally, they demonstrated decreased depression-like behavior in the forced swim test and no change in pain perception in the tail-flick test. Conclusion: The nitrergic system is possibly involved in neural circuitry development that regulates behaviors since blocking perinatal nitric oxide production decreases anxiety- and depression-like behaviors in adult mice.

Acta cir. bras ; 35(3): e202000301, 2020. tab, graf
Article in English | LILACS | ID: biblio-1130626


Abstract Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.

Animals , Male , Rats , Spinal Cord/metabolism , Brain/metabolism , Oxidative Stress/physiology , Hydroxyurea/therapeutic use , Anemia, Sickle Cell/drug therapy , Liver/metabolism , Rats, Wistar , NG-Nitroarginine Methyl Ester , Disease Models, Animal , Anemia, Sickle Cell/physiopathology , Anemia, Sickle Cell/metabolism
Int. braz. j. urol ; 43(2): 356-366, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-840829


ABSTRACT Purpose To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. Materials and Methods C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. Results BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. Conclusion It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.

Animals , Male , Urinary Bladder Neck Obstruction/drug therapy , Nitric Oxide Synthase/antagonists & inhibitors , NG-Nitroarginine Methyl Ester/pharmacology , Enzyme Inhibitors/pharmacology , Lower Urinary Tract Symptoms/drug therapy , Guanidines/pharmacology , Nitric Oxide/antagonists & inhibitors , Pressure , Time Factors , Urination/drug effects , Urination/physiology , Urinary Bladder/drug effects , Urinary Bladder/physiopathology , Urinary Bladder Neck Obstruction/physiopathology , Random Allocation , Reproducibility of Results , Treatment Outcome , NG-Nitroarginine Methyl Ester/therapeutic use , Enzyme Inhibitors/therapeutic use , Guanidines/therapeutic use , Mice, Inbred C57BL , Muscle Contraction/drug effects
Rev. bras. med. esporte ; 22(1): 31-34, jan.-fev. 2016. tab, graf
Article in Portuguese | LILACS | ID: lil-771109


RESUMO Introdução: A capacidade intrínseca para o exercício aeróbico está relacionada com o inotropismo cardíaco. Por outro lado, a participação do óxido nítrico (NO) como mensageiro intracelular sobre a dinâmica do Ca2+ ainda permanece desconhecida em ratos com diferentes capacidades intrínsecas para o exercício. Objetivo: Avaliar se o NO modula diferentemente o transiente intracelular de Ca2+ e liberações espontâneas de Ca2+(sparks) em cardiomiócitos de ratos com diferentes capacidades intrínsecas para o exercício. Métodos: Ratos machos Wistar foram selecionados como desempenho padrão (DP) e alto desempenho (AD), de acordo com a capacidade de exercício até a fadiga, mensurada através de teste de esforço progressivo em esteira. Os cardiomiócitos dos ratos foram utilizados para determinar o transiente intracelular de Ca2+ e Ca2+sparks em microscópio confocal. Para estimar a contribuição do NO foi utilizado o inibidor das sínteses do NO (L-NAME, 100 µM). Os dados foram analisados através de ANOVA two-way seguido do pós-teste de Tukey e apresentados como médias ± EPM. Resultados: Os cardiomiócitos de ratos AD exibiram aumentos na amplitude do transiente de Ca2+ em comparação aos DP. Entretanto, o L-NAME aumentou a amplitude do transiente de Ca2+ somente em ratos DP. Não foram encontradas diferenças na constante de tempo de decaimento do transiente de Ca2+ (t) em cardiomiócitos de ratos com DP e AP, contudo, a administração do L-NAME diminuiu o t em cardiomiócitos em ambos os grupos. cardiomiócitos de ratos AD apresentaram menor amplitude e frequência de Ca2+sparks em comparação ao grupo DP. A administração de L-NAME aumentou a amplitude de Ca2+sparks em cardiomiócitos do grupo AD. Conclusão: O NO modula o transiente de Ca2+ e as sparks de Ca2+ em cardiomiócitos de ratos com diferentes capacidades intrínsecas para o exercício.

ABSTRACT Introduction: The intrinsic capacity to aerobic exercise is associated with cardiac inotropism. On the other hand, the contribution of nitric oxide (NO) as an intracellular messenger on Ca2+ dynamics remains unknown in rats with different intrinsic capacities to exercise. Objective: To evaluate whether NO modulates differently Ca2+ intracellular transient and spontaneous Ca2+ releases (sparks) in cardiomyocytes of rats with different intrinsic capacities to exercise. Methods: Male Wistar rats were selected as standard-performance (SP) and high-performance (HP), according to the exercise capacity until fatigue, assessed through a treadmill progressive stress test. Cardiomyocytes of rats were used to determine Ca2+ intracellular transient and Ca2+ sparks evaluated using confocal microscope. To estimate NO contribution, a NO synthase inhibitor (L-NAME, 100 µM) was used. Data were analyzed through two-way ANOVA followed by Tukey's post hoc test and expressed as means ± SEM. Results: Cardiomyocytes of HP rats exhibited higher Ca2+ transient amplitude compared to SP. However, L-NAME increased Ca2+ transient amplitude only in SP rats. No differences were found in Ca2+ transient decay time constant ( t) in cardiomyocytes of SP and HP rats. However, administration of L-NAME caused reduction of tin cardiomyocytes of both groups. Lower amplitude and frequency of Ca2+ sparks were found in cardiomyocytes of HS rats compared to SP group. Administration of L-NAME increased the amplitude of Ca2+ sparks in cardiomyocytes of the HP group. Conclusion: NO modulates Ca2+ transient and Ca2+ sparks in cardiomyocytes of rats with different intrinsic exercise capacities.

RESUMEN Introducción: La capacidad intrínseca para el ejercicio aeróbico está relacionada con el inotropismo cardiaco. Por otro lado, todavía se desconoce la contribución del óxido nítrico (ON) como mensajero intracelular sobre la dinámica del Ca2+ en ratones con diferentes capacidades intrínsecas para el ejercicio. Objetivo: Evaluar si el ON modula diferencialmente la variación transitoria intracelular de Ca2+ y las liberaciones espontaneas de Ca2+ (sparks) en cardiomiocitos de ratones con diferentes capacidades intrínsecas para el ejercicio. Métodos: Ratones machos Wistar fueron seleccionados como desempeño estándar (DE) y alto desempeño (AD), de acuerdo con la capacidad de ejercicio hasta la fatiga, medida a través del test de fuerza progresiva en la caminadora o cinta eléctrica. Los cardiomiocitos de los ratones fueron utilizados para determinar el tránsito intracelular y sparks de Ca2+ evaluados en microscopio confocal. Para estimar la contribución del ON fue utilizado un inhibidor de síntesis del ON (L-NAME, 100 µM). Los datos fueron analizados a través de un ANOVA two-way seguido de un post-test Tukey y presentados como promedios ± EPM. Resultados: Los cardiomiocitos de ratones AD mostraron aumento en la amplitud de la variación transitoria de Ca2+ en comparación con los DE. Así mismo, el L-NAME incremento la amplitud transitoria de Ca2+ solamente en ratones DE. No se encontraron diferencias en la constante del tiempo de decaimiento de la variación transitoria ( t ) de Ca2+ en cardiomiocitos de ratones DE e AD. Todavía, la administración de L-NAME mostro una reducción en el t en cardiomiocitos de ambos los grupos. Cardiomiocitos de ratones AD presentaron menor amplitud y frecuencia de sparks de Ca2+ en comparación al grupo DE. La administración de L-NAME incrementó la amplitud de sparks de Ca2+ en cardiomiocitos del grupo AD. Conclusión: El ON modula la variación de Ca2+ y sparks de Ca2+ en cardiomiocitos de ratones con diferentes capacidades intrínsecas para el ejercicio.

Acta cir. bras ; 30(5): 345-352, 05/2015. tab, graf
Article in English | LILACS | ID: lil-747028


PURPOSE: To evaluated the effects of L-arginine (a NO donor) and L-NAME (Nw-nitro-L-arginine methyl ester - a NOS inhibitor) on ischemia-reperfusion in rat livers. METHODS: One hundred fifty two male Wistar rats were divided into four groups: control (simulated surgery); hepatic IR; pretreatment with L-arginine plus hepatic IR; and L-NAME plus hepatic IR. The hepatocellular damage was evaluated at the first, third and seventh days after the procedures through the alanine-aminotransferase (ALT) and aspartate-aminotransaminase (AST) levels, as well as histopathological features: vascular congestion (VC); steatosis (STE); necrosis (NEC); and inflammatory infiltration (INF). The mortality rate was also evaluated. RESULTS: The pretreatment with L-NAME significantly worsened the AST levels after hepatic IR (p<0.05) at first day and L-arginine demonstrated an attenuating effect on ALT levels at seventh day (p<0.05). Furthermore, the administration of L-arginine was able to reduce the VC and STE in the seventh day after hepatic IR (p<0.05). The analysis of the mortality rates did not demonstrate any difference between the groups. Nevertheless, there was not effect of L-arginine and L-NAME on the mortality of the animals. CONCLUSION: L-arginine/NO pathway has a role in the hepatic IR because the pretreatment with L-arginine partially had attenuated the hepatocellular damage induced by hepatic IR in rats. .

Animals , Male , Arginine/therapeutic use , Enzyme Inhibitors/therapeutic use , Liver/blood supply , Liver/drug effects , NG-Nitroarginine Methyl Ester/therapeutic use , Reperfusion Injury/prevention & control , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Disease Models, Animal , Liver/pathology , Necrosis , Nitric Oxide Synthase/drug effects , Nitric Oxide Synthase/metabolism , Nitric Oxide/metabolism , Random Allocation , Rats, Wistar , Reference Values , Reproducibility of Results , Time Factors , Treatment Outcome
Arq. gastroenterol ; 51(4): 302-308, Oct-Dec/2014. tab, graf
Article in English | LILACS | ID: lil-732199


Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin) was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α. .

Contexto A inflamação intestinal pode induzir uma redução local nos níveis de oxigênio e ativar uma resposta adaptativa relacionada à expressão de fatores induzíveis por hipóxia (HIFs). O óxido nítrico, um mediador inflamatório bem descrito, pode interferir com a sinalização de hipóxia. Objetivos O objetivo foi avaliar o papel do óxido nítrico na sinalização de hipóxia durante a inflamação colônica. Métodos A colite foi induzida em ratos pela administração única (aguda) ou repetida (com reativações) de ácido trinitrobenzenosulfônico. Adicionalmente, um grupo de ratos de colite com reativações foi também tratado com Nw-Nitro-L-arginina metil éster para inibir a óxido nítrico sintase. A colite foi avaliada através do escore macroscópico e da atividade de mieloperoxidase em amostras de cólon. A hipóxia foi determinada usando uma sonda dependente de oxigênio, o pimonidazol. A expressão de HIF-1α e de fatores induzidos pelo HIF (factor de crescimento endotelial vascular - VEGF e apelina) foi avaliada pela técnica de Western blotting. Resultados A administração única ou repetida de ácido trinitrobenzenosulfônico a ratos induziu colite que foi caracterizada por um alto escore macroscópico e alta atividade de mieloperoxidase. Hipóxia foi observada em ambos os protocolos. Durante a colite aguda, a expressão de HIF-1α não aumentou, enquanto a de VEGF e apelina aumentou. A expressão de HIF-1α esteve inibida durante a colite com reativações e, a expressão de VEGF e apelina não se modificou. O bloqueio com Nw-Nitro-L-arginina metil éster durante a colite com reativações restabeleceu a expressão de HIF-1α, VEGF e ...

Animals , Male , Colitis/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Nitric Oxide/metabolism , Colitis/chemically induced , Hypoxia-Inducible Factor 1, alpha Subunit/analysis , Nitric Oxide/analysis , Rats, Wistar
Acta cir. bras ; 24(2): 107-111, Mar.-Apr. 2009. graf
Article in English | LILACS | ID: lil-511323


PURPOSE: Evaluate polymorphonuclear leukocytes (PMN's) and mononuclear cells (MN's) involvement in the Ehrlich´s solid tumor (ET) growth. METHODS: 90 Swiss mice were inoculated with 10(7) tumor cells (sc), distributed in three groups and treated once a day, via intraperitoneal (ip), with 0.1ml of diluent, L-Arginine (20mg/Kg) or L-NAME (20mg/Kg). After 7, 15 and 30 days of treatment, ten animals of each group were euthanized, the tumor mass was removed, processed and fixed for HE. Later, a morphometric analysis of the total area, parenchyma, necrosis, tumor stroma and PMN's leukocytes and MN's cells influx was performed. RESULTS: The L-Arginine treatment increased PMN's influx in the initial stage, whereas L-NAME reduced it. Our data suggests that NO effect on PMN's migration is dose-dependent. On the other hand, the MN´s cells influx was reduced by L-NAME treatment at all evaluated periods and at the same periods an increase in tumor growth was observed. CONCLUSION: At initial stages of tumor implantation, both PMN's leukocytes and MN's cells act together to control ET development.

OBJETIVO: Avaliar o envolvimento de leucócitos polimorfonucleares (PMN's) e células mononucleares (MN's) no crescimento do Tumor Sólido de Ehrlich (TE). MÉTODOS: 90 camundongos Suíços foram inoculados com 10(7) células tumorais (sc), distribuídos em três grupos e tratados uma vez ao dia, via intraperitoneal (ip), com 0.1ml de diluente, L-Arginina (20mg/Kg) ou L-NAME (20mg/Kg). Após 7, 15 e 30 dias, dez animais de cada grupo foram eutanasiados, a massa tumoral foi removida, processada e corada pela HE. Posteriormente, foi realizada análise morfométrica das áreas total, parênquima, necrose, estroma e influxo de leucócitos PMN's e células MN's. RESULTADOS: O tratamento com L-Arginina favoreceu o influxo de PMN's em períodos iniciais, enquanto o tratamento com L-NAME o reduziu. Nosso estudo sugere que o efeito do ON sobre a migração de PMN's é dose-dependente. Por outro lado, o influxo de células MN´s foi contido pelo tratamento com L-NAME em todos os períodos avaliados, mesmos períodos em que se observou um aumento no crescimento tumoral. CONCLUSÃO: Em fases iniciais do implante tumoral, ambos, leucócitos PMN's e células MN's, atuam juntos no controle do desenvolvimento do TE.

Animals , Male , Mice , Arginine/pharmacology , Carcinoma, Ehrlich Tumor/pathology , Enzyme Inhibitors/pharmacology , Leukocytes, Mononuclear/pathology , NG-Nitroarginine Methyl Ester/pharmacology , Neutrophils/drug effects , Disease Models, Animal , Leukocytes, Mononuclear/physiology , Neutrophils/physiology , Nitric Oxide Synthase/metabolism
Journal of Korean Medical Science ; : 637-640, 2003.
Article in English | WPRIM | ID: wpr-221863


The role of nitric oxide during neonatal sepsis is complex. We tested the hypothesis that nonselective inhibition of nitric oxide synthase with N(w) -nitro-L-arginine methyl ester (L-NAME) is detrimental during the early phase of experimental sepsis in the newborn piglet. Newborn piglets were divided into four groups: 6 in the control group, 6 in the L-NAME control group, 12 in the sepsis group (SG), and 11 in the sepsis with L-NAME group (NS). Sepsis was induced by intravenous injection of 10(8) colony forming units of Escherichia coli. L-NAME 10 mg/kg was given intravenously 60 min before the induction of sepsis. The survival rate of piglets after 4 hr was 27% in NS, while it was 100% in other groups. Systemic hypotension, observed in both SG and NS, were more profound in NS. Leukopenia was observed in both SG and NS. Thrombocytopenia, prolongation of prothrombin time and activated partial thromboplastin time, and increase in thrombin-antithrombin complexes were observed only in NS. Decreased PaO2 /FiO2 ratio, arterial pH and base excess, and increased blood lactate levels observed in both SG and NS, but were more profound in NS. These findings suggest that nonselective inhibition of nitric oxide synthase with L-NAME is detrimental during the early phase of experimental neonatal sepsis.

Animals , Animals, Newborn , Enzyme Inhibitors/pharmacology , Escherichia coli/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Sepsis/drug therapy , Swine , Time Factors
Korean Journal of Otolaryngology - Head and Neck Surgery ; : 741-746, 2002.
Article in Korean | WPRIM | ID: wpr-654571


BACKGROUND AND OBJECTIVES: Nitric oxide has been suggested to play an important role in the pathogenesis of cisplatin ototoxicity. L-NAME (NG-Nitroarginine Methyl Ester) is an inhibitor of nitric oxide synthase. MK-801 (Dizocilpine Maleate) is a NMDA receptor antagonist. To evaluate a role of nitric oxide in cisplatin ototoxicity, we investigated whether L-NAME and MK-801 can block the cisplatin ototoxicity in guinea pigs. MATERIALS AND METHOD: In the Group 1, normal saline was injected intraperitoneally as a control group. Group 2, 3, 4, and 5 were injected intraperitoneally as described in the following: Group 2, cisplatin only; Group 3, L-NAME+isplatin; Group 4, MK-801+cisplatin; Group 5, L-NAME+K-801+cisplatin. Using an auditory brainstem response, hearing threshold was tested before cisplatin administration and 5 days after cisplatin injection in each group. The morphological changes of the cochlea were observed by scanning electron microscopy. RESULTS: In the Group 2, a significant hearing loss was observed comparing to Group 1. In contrast , Group 3, 4, and 5 did not demonstrate any significant hearing loss compared to Group 1. In the scanning electron microscopy, the Group 2 showed distorsion and loss of stereocilia of the hair cells. However, the Group 1, 3, 4, and 5 demonstrated well preserved cochlear hair cell morphology. CONCLUSION: Hearing loss induced by ototoxicity of cisplatin was prevented by L-NAME and MK-801. This study suggests that NO may mediate cisplatin ototoxicity.

Animals , Cisplatin , Cochlea , Dizocilpine Maleate , Evoked Potentials, Auditory, Brain Stem , Guinea Pigs , Guinea , Hair , Hearing , Hearing Loss , Microscopy, Electron, Scanning , N-Methylaspartate , NG-Nitroarginine Methyl Ester , Nitric Oxide , Nitric Oxide Synthase , Stereocilia
Journal of Korean Society of Endocrinology ; : 719-728, 1999.
Article in Korean | WPRIM | ID: wpr-46208


BACKGROUND: NO (nitric oxide), derived from L-arginine through the action of nitric oxide synthase (NOS), is a short-lived free radical transmitting cellular signals for vasodilation, neurotransmission, and cytotoxicity. Recently, this molecule has been reported to be involved in the various glandular secretion. Although the relationship between NO and the pancreatic endocrine secretion has been widely investigated, the role of NO on insulin secretion has not been elucidated. Therefore, the present study was designed to reveal the precise action of NO on the secretion and synthesis of insulin following administration of NAME (L-NG -nitroarginine methyl ester) or L-arginine using immunocytochemistry and in situ hybridization techniques. METHODS: NAME or L-arginine was administered into jugular vein of the male Sprague-Dawley rat (180~200 g, b,w.) exhibiting normoglycemia (80~120mg/dL). Blood glucose concentrations were measured at intervals of 30 minutes for 2 hours after drug treatment. The pancreatic tissues were taken out at 30 and 90 minutes following drugs administration for insulin immunocytochemistry and in situ hybridization. RESULTS: Both NAME and L-arginine treatments diminished blood glucose levels. The decrease of blood glucose level was more prominent in NAME-treated rats than that of L-arginine. Insulin immunoreactivity in drugs-treated rat pancreas decreased compared to that in normal control, while the expression of insulin mRNA was significantly increased. CONCLUSION: On the basis of present study, it is concluded that the transient changes of NO con-centration, regardless of increase or decrease, in Langerhans islet might act as a potent stimulant in insulin secretion and its synthesis.

Animals , Humans , Male , Rats , Arginine , Blood Glucose , Immunohistochemistry , In Situ Hybridization , Insulin , Jugular Veins , Nitric Oxide Synthase , Nitric Oxide , Pancreas , Rats, Sprague-Dawley , RNA, Messenger , Synaptic Transmission , Vasodilation
Korean Journal of Anatomy ; : 299-307, 1998.
Article in Korean | WPRIM | ID: wpr-650831


nitric oxide (NO) has been known as a cytotoxic free radical or a messenger molecule in various tissues of the body. Recently, this small molecule was reported to be associated with secretory function of glandular tissues. Although it is very likely that NO modulates the pancreatic secretion, little is known about its accurate mechanism of action. We, thus, attempted to reveal the action of NO on insulin secretion by analyzing insulin immunoreactivity and its mRNA expression in the pancreatic islet of the rats treated with NAME (L-N(G)-nitroarginine methyl ester), a NOS inhibitor. Male Sprague-Dawley rats (150~200 g, body weight) with normal blood glucose level (80~120 mg/dl) were assign-ed into normal control group and the experimental ones. NAME was injected into jugular vein of the rats by cannula-tion using polyethylene tube. We have examined blood glucose level at every 30 minutes for 2 hours after NAME injection. Other rats were killed at every 30 minutes for 2 hours following the NAME treatment, and the pancreatic tissues were taken in order to analyze the changes of insulin contents and insulin mRNA expression with the techniques of immunocytochemistry and in situ hybridization. The present experiments showed that intrapancreatic NO influence insulin secretion in the pancreatic islets. Blood glucose concentration was decreased for initial 90 minutes after NAME injection, then, recovered towards normogly-cemic state. Immunocytochemical staining demonstrated that a slight increase of insulin immunoreactivity was found in some Langerhans islets of the NAME-treated rats. On the contrary, we found a considerable increase of insulin mRNA expression in the NAME-treated rats compared to the control one. Based on the results of the present experiments, we suggest that NO is a potent and endogenous modulator of insulin secretion, and a lowered level of NO in pancreatic tissue stimulates insulin synthesis in beta cells by promoting transcrip-tion of insulin DNA.

Animals , Humans , Male , Rats , Blood Glucose , DNA , Immunohistochemistry , In Situ Hybridization , Insulin , Islets of Langerhans , Jugular Veins , Nitric Oxide , Pancreas , Polyethylene , Rats, Sprague-Dawley , RNA, Messenger
Chinese Journal of Anesthesiology ; (12)1996.
Article in Chinese | WPRIM | ID: wpr-522936


Objective To investigate the effect of pre-emptive intrathecal (IT) administration of L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor on calcitonin gene-related peptide (CGRP) expression in the dorsal horn of spinal cord in a rat model of neuropathic pain. Methods Ninety-six female adult SD rats weighing 220-310 g were randomly divided into four groups with 24 animals in each group : group A received IT 0.9% NaCl 15 min before sham operation; group B received IT 0.9% NaCl 15 min before right sciatic nerve ligation; group C received IT L-NAME 250 mg in 10?l 15 min before sham operation and group D received IT L-NAME 250 ?g in 10 ?l15 min before sciatic nerve ligation. The animals were anesthetized with intraperitoneal pentobarbital 50 mg?kg-1. A PE-10 catheter was placed in subarachnoid space with the tip of the catheter reaching the lumbar enlargement region. The animals were allowed to recover for 3-4 days and only those waking normally were used in the study. Right sciatic nerve was exposed and four loose ligatures were placed on the sciatic nerve according to the method described by Bennet. In sham operation the sciatic nerve was exposed but not ligated. The animals were sacrificed on the 1 st, 4 th, 7 th and 14 th day after operation. The lumbar segment of spinal cord was immediately removed. The CGRP expression in the ligated-side dorsal horn was assessed with immuno-histochemistry technique. Results In group B and D CGRP expression in the ligated side dorsal horn was significantly increased on the 4th, 7th and 14th day after operation as compared with that in group A. There was no significant difference in the CGRP expression in the ligated side dorsal horn between group A and C as well as between B and D. Conclusion Pre-emptive IT administration of L-NAME cannot inhibit the increase in CGRP expression in dorsal horn induced by peripheral nerve injury, suggesting that the neuropathic pain mediated by NO is not related to the release of calcitonin gene-related peptide.

Chinese Journal of Anesthesiology ; (12)1995.
Article in Chinese | WPRIM | ID: wpr-520119


Objective To investigate the effect of intrathecal (IT) administration of L-NAME , a nonselective nitric oxide synthase (NOS) inhibitor, on c-fos expression in spinal cord induced by neuropathic pain. Methods Eighty-four female SD rats weighing 220-310g, which showed no signs of never injury 3 to 4 days after IT catheterization with the tip of catheter reaching the lumbar region, were divided into 4 groups at random: group A received IT 0.9% NaCl 10?g 15min before sham operation ( n = 16); group B received IT 0.9% NaCl 10?l 15min before ligation of sciatic nerve ( n =24); group C received IT L-NAME 10?l (250?g) 15min before sham operation ( n = 16); group D received IT L-NAME 10?l (250?g) 15min before ligation of sciatic nerve (n =24) . The animal in each group were further divided into 4 subgroups ( n = 4-6) and sacrificed on 1st, 3rd, 7th and 14th day after operation. In addition 4 rats which had received no operation of any kind were sacrificed and served as control. The c-fos expression in ipsilateral dorsal horn of spinal cord was detected by immunohistochemistry technique. Results In normal rats in control group (no IT catheterization, no operation) there were only a few fos-positive neurone (3.4? 0.9). The c-fos expression in the ipsilateral dorsal horn of spinal cord greatly increased both in group A and B. In group B there were more fos-positive neurons (FLIN) in the ipsilateral dorsal horn on the 3rd, 7th and 14th day as compare with group A. With pre-emptive intrathecal administration of L-NAME, the increase in ipsilateral c-fos expression induced by ligation of sciatic nerve was inhibited. In group D the number of fos-positive neurons in ipsilateral dorsal horn decreased by 53.8%, 57.1% and 43.2% on the 3rd, 7th and 14th day after operation as compare with group B. On the 1st day afteroperation there was no difference-in FLIN in the ipsilateral dorsal horn between group B and D. Conclusion Nitric oxide plays an important role in mediating the neuropathic pain which can be effectively attenuated or prevented by pre-emptive IT administration of L-NAME.