A influência do oxido nítrico na fisiopatologia da neuropatia glaucomatosa / The influence of nitric oxide on the pathophysiology of glaucomatous neuropathy

Resumo O oxido nitrico (NO) é um fator relaxante derivado do endotélio e um potente vasodilatador que impacta em vários sistemas em todo o corpo. Estudos comprovam que o fluxo sanguíneo ocular basal é regulado pelo NO, sendo um importante regulador da homeostase, especialmente dentro dos tecidos uveais. A disfunção da produção de NO seria associado ao glaucoma através da alteração da perfusão da cabeça do nervo óptico associado ao aumento da pressão intraocular devido um sistema de drenagem trabecular deficiente. O NO tornou-se uma molécula atraente para o tratamento do glaucoma devido a possibilidade de modulação da drenagem trabecular, abaixando a pressão intraocular e ação neuroprotetora melhorando a perfusão sanguínea na cabeça do nervo óptico.

Abstract Nitric Oxide (NO) is a relaxing endothelium-derived factor and a potent vasodilator that impacts various systems throughout the body. Proven studies of basal ocular blood flow are regulated by NO, being an important regulator of homeostasis, especially within the uveal tissues. The dysfunction of the production associated with glaucoma due to alteration of the optic nerve head associated to the increase of the intraocular pressure by a deficient trabecular meshwork. NO became an attractive molecule for the treatment of glaucoma due to a modulation of the trabecular meshwork, lowering the neuroprotective intra and ocular pressure for a blood surgery in the head of the optic nerve.

Effect of nitric oxide inhibitor and donor substances on the infammatory process caused by endodontic irrigants

Nitric oxide (NO) has been considered a key molecule in infammation. OBJECTIVE: The aim of this study was to evaluate the effect of treatment with L-NAME and sodium nitroprussiate, substances that inhibit and release NO, respectively, on tissue tolerance to endodontic irrigants. MATERIAL AND METHODS: The vital dye exudation method was used in a rat subcutaneous tissue model. Injections of 2 percent Evans blue were administered intravenously into the dorsal penial vein of 14 male rats (200-300 g). The NO inhibitor and donor substances were injected into the subcutaneous tissue in the dorsal region, forming two groups of animals: G1 was inoculated with L-NAME and G2 with sodium nitroprussiate. Both groups received injections of the test endodontic irrigants: acetic acid, 15 percent citric acid, 17 percent EDTA-T and saline (control). After 30 min, analysis of the extravasated dye was performed by light absorption spectrophotometry (620 nm). RESULTS: There was statistically signifcant difference (p<0.05) between groups 1 and 2 for all irrigants. L-NAME produced a less intense infammatory reaction and nitroprussiate intensifed this process. CONCLUSIONS: Independently of the administration of NO inhibitors and donors, EDTA-T produced the highest irritating potential in vital tissue among the tested irrigating solutions.

Donador exógeno de óxido nítrico en la respuesta inflamatoria hepática y hemodinámica después de choque hemorrágico / Exogenous nitric oxide donor in the liver inflammatory and hemodynamic response after hemorrhagic shock

BACKGROUND: Hemorrhagic shock (HS) results in oxidative stress to cells and in the induction of the inflammatory response, with an increased expression of a number of proinflammatory mediators and cytokines. We tested the ability of the nitric oxide (NO) donor sodium nitroprusside (NP) to reduce tissue injury in a rodent model of uncontrolled hemorrhagic shock. METHODS: Seventy two Sprague Dawley rats weighing 250-300 g were subjected to a model of uncontrolled hemorrhagic shock. Four groups of animals were included (n = 18 per group): sham/saline, sham/NP, shock/saline, shock/NP. Experimental design consisted of the development of hemorrhagic shock (3 ml/100 g) in a 15-min period, tail amputation (75%) and drug administration at 30 min, fluid resuscitation (FR) with Ringer's lactate (RL) solution to reach a mean arterial pressure (MAP) of 40 mmHg, a hospital phase of 60 min with hemostasis and FR with LR solution to reach a MAP of 70 mmHg, and a 3-day observation phase. Treatment at the beginning of resuscitation included either normal saline (groups 1, 3) or NP (0.5 mg/kg) (groups 2, 4). The following parameters were evaluated: fluid requirements for resuscitation, liver injury tests, liver tissue myeloperoxidase (MPO), liver histology, and 3-day survival. RESULTS: NP significantly reduced fluid requirements for resuscitation (p = 0.0001). We also observed an improved statistically significant difference in tests demonstrating hepatic injury (p = 0.0001), neutrophil infiltration as evidences by liver MPO (p <0.05), and histology studies (p = 0.001). Survival was also increased from 40% in controls to 60% with NP treatment. CONCLUSIONS: These data suggest that excess NO mediates hemorrhage-induced liver injury, and that the suppression of NO with NP may reduce the pathological consequences of severe hemorrhage, possibly by scavenging superoxide (O(2)(-)), thus limiting the production of more aggressive radicals.

Preventive effects of nitroglycerine on glucocorticoid-induced osteoporosis in growing rats / 华中科技大学学报（医学）（英德文版）

The preventive effects of nitroglycerine (NG) on glucocorticoid-induced osteoporosis in growing rats were studied. Three-month-old female Wistar rats were randomly divided into control group (CON), dexamethasone group (DXM), DXM plus a low dose NG group (NG-L), DXM plus a middle dose NG group (NG-M) and DXM plus a high dose NG group (NG-H), 8 rats in each group. The rat model of osteoporosis was developed by intramuscular injection of dexamethasone twice a week. NG 0.2, 0.4 and 1.0 mg/kg was administered by oral gavages to the treatment groups every day for 12 weeks. Rats in CON group and DXM group were treated with normal saline of the same amount. After the treatment, the bone mineral density (BMD) and bone metabolism-associated biochemical markers were determined. Compared with CON group, BMD of lumbar spine and femur in DXM group was decreased significantly (P<0.05 and P<0.01 respectively), blood BGP levels and NO levels reduced (both P<0.01), and TRAP level increased (P<0.05). As compared with DXM group, BMD, serum BGP and NO were increased, and TRAP decreased in NG-L group and NG-M group, but had no significant difference in comparison to CON group. All the markers other than serum NO and TRAP levels had no significant difference between NG-H group and DXM group. It was concluded that low or middle doses of NG could prevent glucocorticoid-induced bone loss in growing rats, but high dose of NG could not. Supplement with NO donor could be considered as a preventive treatment for glucocorticoid-induced osteoporosis in a developing skeleton.

The cytoprotective effect of a nitric oxide donor drug on gastric mucous membrane of rats treated with ketoprofen, a non-steroidal anti-inflammatory drug / Efeito citoprotetor de uma droga doadora de óxido nítrico na membrana da mucosa gástrica de ratos tratados com o antiinflamatório não-esteróide - o cetoprofeno

BACKGROUND: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent. AIM: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment. METHODS: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration. RESULTS: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared...

RACIONAL: Drogas antiinflamatórias não-esteróides são consideradas, atualmente, importante grupo de medicamentos, com ampla variedade de uso terapêutico, em diferentes áreas da medicina moderna. Apesar de seus efeitos benéficos para o paciente, apresentam grande incidência de efeitos colaterais, principalmente no trato gastrointestinal. Os mecanismos fisiopatológicos de lesões induzidas por essas drogas e os mecanismos de defesa da mucosa gástrica tornaram-se uma importante linha de pesquisa médica, especialmente procurando avaliar o papel de óxido nítrico como agente citoprotetor. OBJETIVO: Estudar uma droga doadora de ácido nítrico - o dinitrato de isossorbida - e sua ação citoprotetora da mucosa gástrica de ratos submetidos ao tratamento com uma droga antiinflamatória - o cetoprofeno. MÉTODOS: Ratos machos adultos previamente submetidos a jejum de 24 horas, foram divididos em três grupos: a) grupo I (controle): animais, que receberam apenas solução salina isotônica via intragástrica, por gavagem e via endovenosa; b) grupo II (cetoprofeno-controle): animais que receberam solução salina via intragástrica por gavagem e cetoprofeno via endovenosa, e c) grupo III (nitrato/cetoprofeno): animais que receberam solução de 2 mM de dinitrato de isossorbida a via intragástrica por gavagem e cetoprofeno via endovenosa. Esses grupos foram, posteriormente, submetidos a exames macroscópico, microscópico e bioquímico, avaliando-se os seguintes parâmetros: a) determinação do índice de lesão gástrica; b) determinação da espessura da camada do muco secretor; c) determinação da concentração de ácido nítrico x tecidual, e d) determinação da concentração do malondialdeído tecidual. RESULTADOS: Encontrou-se menor índice de lesão gástrica nos animais do grupo III (nitrato), assim como maior espessura da camada do muco secretor nos animais deste grupo, do que nos animais do grupo II (cetoprofeno). A variação da concentração do ácido nítrico x tecidual foi semelhante nos três grupos. A taxa...

Effect of systemically administered nitric oxide donor, sodium nitroprusside on picrotoxin-induced convulsions in rats.

Nitric oxide (NO), the gaseous neurotransmitter has been reported to have an endogenous anticonvulsant property. This has prompted proposals to develop NO donors as anticonvulsant drugs. In the present study, the effect of NO donor, sodium nitroprusside (SNP) on picrotoxin (PCT)-induced convulsions was investigated. A convulsant dose of PCT (5 mg/kg) was administered 5, 10, 15 and 30 min after intraperitoneal injection of graded doses (0.7, 1.25 and 2.5 mg/kg) of SNP. SNP at doses 0.7 and 1.25 mg/kg increased dose dependently the severity of PCT-induced convulsions. But, pretreatment with the higher dose (2.5 mg/kg) of SNP was protective against PCT-induced convulsions. However, post treatment (5 and 10 min) with the same dose exacerbated convulsions and caused death of the animals. These results indicate that the vasodilator effect of SNP and an increased perfusion of PCT into brain may be responsible for the proconvulsant action of SNP. A decreased entry of PCT because of marked vasodilation and hypotension has been speculated for an inhibition of convulsions in animals pretreated with a higher dose of SNP. In conclusion, the results reveal the non-suitability of SNP to be developed as an anticonvulsant.