Nitric oxide-releasing nanomaterials: from basic research to potential biotechnological applications in agriculture.

Nitric oxide (NO) is a multifunctional gaseous signal that modulates the growth, development and stress tolerance of higher plants. NO donors have been used to boost plant endogenous NO levels and to activate NO-related responses, but this strategy is often hindered by the relative instability of donors. Alternatively, nanoscience offers a new, promising way to enhance NO delivery to plants, as NO-releasing nanomaterials (e.g. S-nitrosothiol-containing chitosan nanoparticles) have many beneficial physicochemical and biochemical properties compared to non-encapsulated NO donors. Nano NO donors are effective in increasing tissue NO levels and enhancing NO effects both in animal and human systems. The authors believe, and would like to emphasize, that new trends and technologies are essential for advancing plant NO research and nanotechnology may represent a breakthrough in traditional agriculture and environmental science. Herein, we aim to draw the attention of the scientific community to the potential of NO-releasing nanomaterials in both basic and applied plant research as alternatives to conventional NO donors, providing a brief overview of the current knowledge and identifying future research directions. We also express our opinion about the challenges for the application of nano NO donors, such as the environmental footprint and stakeholder's acceptance of these materials.

Flavonoids and saponins from Passiflora edulis f. edulis leaves (purple passion fruit) and its potential anti-inflammatory activity.

OBJECTIVES: The objective of this work was to evaluate the anti-inflammatory activity of the aqueous extract, fractions and major compounds, which are isolated and identified from Passiflora edulis f. edulis (purple passion fruit) leaves extract. METHODS: For the isolation of the major compounds, reversed-phase chromatography and normal phase countercurrent chromatography were used. The separation was followed by thin layer chromatography and HPLC-DAD-ELSD. One-dimensional and two-dimensional NMR and ESI-TOF-MS/MS were used for structural elucidation. The anti-inflammatory activity was evaluated on a TPA multiple dose model of skin chronic inflammation in mice. Additionally, myeloperoxidase (MPO) and nitric oxide synthase (NOS) activity assays were performed as possible mechanisms of action studies. KEY FINDINGS AND CONCLUSIONS: The study of the butanolic fraction mainly showed the presence of saponins and flavonoids. Three minor flavonoids were detected; and three known saponins, cyclopassiflosides IX, XI and III were isolated and identified. This is the first unequivocal report of the presence of these compounds in P. edulis f. edulis leaves. The most favourable results of anti-inflammatory activity were obtained for the flavonoid-rich fraction. All the fractions and isolated compounds evaluated, presented high percentages of inhibition of nitric oxide synthase activity.

Probiotic Properties and Immunomodulatory Activity of Lactobacillus Strains Isolated from Dairy Products.

Lactobacilli species are an effective biotherapeutic alternative against bacterial infections and intestinal inflammatory disorders. However, it is important to evaluate their beneficial properties, before considering them as probiotics for medical use. In this study we evaluated some probiotic properties of Lactobacillus rhamnosus GG, Lactobacillus rhamnosus KLSD, Lactobacillus helveticus IMAU70129, and Lactobacillus casei IMAU60214 previously isolated from dairy products and as control Lactobacillus casei Shirota. Experimental evaluations revealed that all strains expressed hydrophobicity (25-40%), auto-aggregation (55-60%), NaCl tolerance (1-4%), adhesion to Caco-2 cells (25-33%), partial inhibition on adherence of Escherichia coli ATCC 35218, Salmonella Typhimurium ATCC 14028, and Staphylococcus aureus ATCC 23219. Cell-free supernatants (CFS) of Lactobacilli also inhibit growth of these pathogens. In immunomodulatory properties a reduction of interleukin-8 (IL-8) and nitric oxide (NO) release was observed in assays with Caco-2 cells stimulated with interleukin-1ß (1 ng/mL), or lipopolysaccharide (0.1 µg/mL). On the other hand, the damage induced to Caco-2 cells with sodium dodecyl sulfate (SDS) was attenuated when the cultured cells were pretreated with L. rhamnosus KLDS, L. helveticus IMAU70129 and L. casei IMAU60214. These Lactobacilli possess probiotic properties determined by both an antagonistic activity on pathogenic bacteria and reduction in the inflammatory response of cells treated with SDS, a pro-inflammatory stimulant.

Neuronal Parasitism, Early Myenteric Neurons Depopulation and Continuous Axonal Networking Damage as Underlying Mechanisms of the Experimental Intestinal Chagas' Disease.

There is a growing consensus that the balance between the persistence of infection and the host immune response is crucial for chronification of Chagas heart disease. Extrapolation for chagasic megacolon is hampered because research in humans and animal models that reproduce intestinal pathology is lacking. The parasite-host relationship and its consequence to the disease are not well-known. Our model describes the temporal changes in the mice intestine wall throughout the infection, parasitism, and the development of megacolon. It also presents the consequence of the infection of primary myenteric neurons in culture with Trypanosoma cruzi (T. cruzi). Oxidative neuronal damage, involving reactive nitrogen species induced by parasite infection and cytokine production, results in the denervation of the myenteric ganglia in the acute phase. The long-term inflammation induced by the parasite's DNA causes intramuscular axonal damage, smooth muscle hypertrophy, and inconsistent innervation, affecting contractility. Acute phase neuronal loss may be irreversible. However, the dynamics of the damages revealed herein indicate that neuroprotection interventions in acute and chronic phases may help to eradicate the parasite and control the inflammatory-induced increase of the intestinal wall thickness and axonal loss. Our model is a powerful approach to integrate the acute and chronic events triggered by T. cruzi, leading to megacolon.

The NO-donor MPC-1011 stimulates angiogenesis and arteriogenesis and improves hindlimb ischemia via a cGMP-dependent pathway involving VEGF and SDF-1α.

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is an important cause of morbidity and mortality with little effective medical treatment currently available. Nitric oxide (NO) is crucially involved in organ perfusion, tissue protection and angiogenesis. METHODS: We hypothesized that a novel NO-donor, MPC-1011, might elicit vasodilation, angiogenesis and arteriogenesis and in turn improve limb perfusion, in a hindlimb ischemia model. Hindlimb ischemia was induced by femoral artery ligation in Sprague-Dawley rats, which were randomized to receive either placebo, MPC-1011, cilostazol or both, up to 28 days. Limb blood flow was assessed by laser Doppler imaging. RESULTS: After femoral artery occlusion, limb perfusion in rats receiving MPC-1011 alone or in combination with cilostazol was increased throughout the treatment regimen. Capillary density and the number of arterioles was increased only with MPC-1011. MPC-1011 improved vascular remodeling by increasing luminal diameter in the ischemic limb. Moreover, MPC-1011 stimulated the release of proangiogenic cytokines, including VEGF, SDF1α and increased tissue cGMP levels, reduced platelet activation and aggregation, potentiated proliferation and migration of endothelial cells which was blunted in the presence of soluble guanylyl cyclase inhibitor LY83583. In MPC-1011-treated rats, Lin-/CD31+/CXCR4+ cells were increased by 92.0% and Lin-/VEGFR2+/CXCR4+ cells by 76.8% as compared to placebo. CONCLUSIONS: Here we show that the NO donor, MPC-1011, is a specific promoter of angiogenesis and arteriogenesis in a hindlimb ischemia model in an NO-cGMP-VEGF- dependent manner. This sets the basis to evaluate and confirm the efficacy of such therapy in a clinical setting in patients with PAD and impaired limb perfusion.

Nesiritide protects endothelial function after balloon-induced trauma in the iliac artery in rabbits

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen

Participation of NO in the vasodilatory action of isoespintanol / Participación de NO en la acción vasodilatadora del isoespintanol

Background: accumulating evidence suggests that natural compounds and specifically monoterpenes exert a vasodilator action. Objetive: to investigate the vascular effects of isoespintanol (2-isopropil-3,6-dimetoxi-5-metilfenol, ISO) monoterpene isolated from the leaves of Oxandra cf xylopioides. Methods: thoracic aortic rings isolated from Wistar rats were contracted with KCl 80 mM and then relaxed by exposure to Ca2+-free solution in absence and in presence of ISO 0.6 mg/mL. The force/tissue ratio (F/W) and the time to obtain 50% of relaxation (T-50) were used to assess the maximal contractile response and the relaxation, respectively. To examine the participation of NO additional experiments were performed under inhibition of nitric oxide synthase with L-NAME (L-NG-Nitroarginine methyl ester). Results: ISO significantly decreased the F/W ratio (257 ± 19 vs. 360 ± 18) and did not change T-50. In presence of L-NAME the effects of ISO on contractile response was abolished. Conclusions: these results demonstrate that ISO exerts a vasodilator effect through NO-dependent pathways and suggest that an inhibition of calcium influx could be the involved mechanism

Antecedentes: la evidencia acumulada sugiere que los compuestos naturales, especialmente monoterpenos, ejercen una acción vasodilatadora. Objetivo: investigar los efectos vasculares del monoterpeno isoespintanol (2-isopropil-3,6-dimetoxi-5-metilfenol, ISO) aislado de hojas de Oxandra cf xylopioides. Métodos: anillos de aorta torácica aislados de ratas Wistar fueron contraídas con cloruro de potasio 80 mM y luego relajadas por exposición a una solución libre de Ca2+ en ausencia y presencia de isoespintanol 0,6 µg/mL. El radio fuerza/tejido (F/T) y el tiempo para obtener 50% de relajación (T50) se usaron para lograr la máxima respuesta contráctil y de relajación, respectivamente. Para evaluar la participación del óxido nítrico, se realizaron experimentos adicionales bajo la inhibición de la óxido nítrico sintetasa con L-NAME (L-NG-éster metílico de nitroarginina). Resultados: Isoespintanol disminuyó el radio F/W significativamente (257 ± 19 vs. 360 ± 18) y no cambió T-50. En presencia de L-NAME, los efectos del isoespintanol en la respuesta contráctil fueron suprimidos. Conclusiones: Estos resultados demuestran que el isoespintanol ejerce un efecto vasodilatador a través de vías NO dependientes y sugiere que la inhibición de la entrada de calcio puede ser el mecanismo involucrado.

Arginine and citrulline for the treatment of MELAS syndrome.

MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes aspect of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS syndrome.

Arginine and Citrulline for the Treatment of MELAS Syndrome

Abstract Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes' aspects of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS syndrome.

Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels.

Thyroid peroxidase (TPO) is essential for thyroid hormone synthesis mediating the covalent incorporation of iodine into tyrosine residues of thyroglobulin process known as organification. Thyroid-stimulating hormone (TSH) via cAMP signaling is the main hormonal regulator of TPO gene expression. In thyroid cells, TSH-stimulated nitric oxide (NO) production inhibits TSH-induced thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Indeed, NO donors downregulate TSH-induced iodide accumulation and organification in thyroid cells. Here, using FRTL-5 thyroid cells as model, we obtained insights into the molecular mechanism underlying the inhibitory effects of NO on iodide organification. We demonstrated that NO donors inhibited TSH-stimulated TPO expression by inducing a cyclic guanosine monophosphate-dependent protein kinase-mediated transcriptional repression of the TPO gene. Moreover, we characterized the FoxE1 binding site Z as mediator of the NO-inhibited TPO expression. Mechanistically, we demonstrated that NO decreases TSH-induced FoxE1 expression, thus repressing the transcripcional activation of TPO gene. Taken together, we provide novel evidence reinforcing the inhibitory role of NO on thyroid cell function, an observation of potential pathophysiological relevance associated with human thyroid pathologies that come along with changes in the NO production.

Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection.

Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α and TGF-ß) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-ß and caused over-expression of CD36 and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated).

Flavonoids modulate the proliferation of Neospora caninum in glial cell primary cultures.

Neospora caninum (Apicomplexa; Sarcocystidae) is a protozoan that causes abortion in cattle, horses, sheep, and dogs as well as neurological and dermatological diseases in dogs. In the central nervous system of dogs infected with N. caninum, cysts were detected that exhibited gliosis and meningitis. Flavonoids are polyphenolic compounds that exhibit antibacterial, antiparasitic, antifungal, and antiviral properties. In this study, we investigated the effects of flavonoids in a well-established in vitro model of N. caninum infection in glial cell cultures. Glial cells were treated individually with 10 different flavonoids, and a subset of cultures was also infected with the NC-1 strain of N. caninum. All of the flavonoids tested induced an increase in the metabolism of glial cells and many of them increased nitrite levels in cultures infected with NC-1 compared to controls and uninfected cultures. Among the flavonoids tested, 3',4'-dihydroxyflavone, 3',4',5,7-tetrahydroxyflavone (luteolin), and 3,3',4',5,6-pentahydroxyflavone (quercetin), also inhibited parasitophorous vacuole formation. Taken together, our findings show that flavonoids modulate glial cell responses, increase NO secretion, and interfere with N. caninum infection and proliferation.

[Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients]. / Níveis de óxido nítrico mais elevados estão associados à atividade da doença em pacientes egípcios com artrite reumatoide.

BACKGROUND: Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage. OBJECTIVES: To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity. METHODS: 80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method. RESULTS: A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I. CONCLUSION: There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status.

Níveis de óxido nítrico mais elevados estão associados à atividade da doença em pacientes egípcios com artrite reumatoide / Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients

Introdução O estresse oxidativo produzido no interior de articulações inflamadas pode produzir fenômenos autoimunes e destruição articular. As espécies radicais com atividade oxidativa, incluindo espécies reativas de nitrogênio, representam mediadores de inflamação e de lesão cartilaginosa. Objetivos Avaliar o óxido nítrico sérico como marcador de estresse oxidativo em pacientes egípcios com artrite reumatoide e sua relação com a atividade da doença. Métodos 80 com artrite reumatoide foram divididos em dois grupos, de acordo com a pontuação DAS28: Grupo I: 42 pacientes com doença ativa, e Grupo II: 38 pacientes com doença inativa. Quarenta indivíduos equiparados por idade e gênero foram incluídos como grupo controle (Grupo III). Foram realizados exames laboratoriais de rotina e o óxido nítrico foi medido usando Elisa. Radiografias simples das mãos foram feitas para a pontuação do estado radiológico utilizando o método de Sharpe. Resultados A comparação do nível sérico de óxido nítrico entre os três grupos mostrou uma diferença altamente significativa (p < 0,001). Obtiveram-se níveis significativamente mais elevados entre os pacientes com artrite reumatoide em comparação com os controles. Os níveis mais elevados foram obtidos em pacientes com a doença ativa (média±DP 82,38±20,46) em comparação com aqueles com a doença inativa (35,53±7,15). O óxido nítrico no Grupo I exibiu uma correlação positiva significativa com a rigidez matinal (r=0,45), artrite (r=0,43), contagem de plaquetas (r=0,46), velocidade de hemossedimentação (r=0,83), proteína C-reativa (r=0,76) e Índice de Atividade de Doença (r=0,85). O óxido ...

Background Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage. Objectives To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity. Methods Eighty patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method. Results A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I. Conclusion There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status. .

Nitric oxide inhibitory activity of hydrogenated synthetic analogues of furanonaphthoquinones isolated from Tabebuia spp

Objective: to describe the synthesis of analogues of furanonaphthoquinones isolated from Tabebuia genus and their inhibitory effect on nitric oxide production. Methods: a series of six derivatives were prepared through cycloaddition reactions and the products characterized by spectroscopy methods. The biological activity was evaluated measuring their effect on the pro-inflammatory mediator production in macrophages RAW 264.7 induced with lipopolysaccharides. To prevent compounds from interfering with cellular viability, their cytotoxic effect was determined using methyl tetrazolium assay. Additionally, scavenging effect was in vitro measured. Results: FNQ1, FNQ2, and FNQ5 derivatives showed potent concentration-depending inhibitory effect on nitric oxide production, with an IC50 value lower than 2 µM concentration at which they did not have toxic or scavenging effects. FNQ5 was the most active and selective derivative. Conclusions: this is the first paper concerning the anti-inflammatory potential of tested synthetic compounds. Our results indicated that FNQ5 might be considered as useful potential anti-inflammatory molecule to treat inflammatory diseases related with nitric oxide overproduction(AU)

Objetivo: describir la síntesis de análogos de furanonaftoquinonas aisladas del género Tabebuia y su efecto inhibidor en la producción de óxido nítrico. Métodos: se obtuvo una serie de seis derivados a través de reacciones de cicloadición y se caracterizaron los productos por métodos espectroscópicos. Se evaluó la actividad biológica por su efecto en la producción del mediador proinflamatorio en macrófagos RAW 264.7 activados con lipopolisacárido. Para asegurar que los compuestos no interfirieran con la viabilidad celular, se evaluó su efecto citotóxico empleando el ensayo de metiltetrazolio. Adicionalmente, se evaluó el efecto captador del radical in vitro. Resultados: los derivados FNQ1, FNQ2 y FNQ5 demostraron potente efecto inhibitorio en la producción de óxido nítrico de manera concentración-dependiente, con un valor de CI50 menor que 2 µM, concentración a la que no ejercieron efectos tóxicos o captadores de radicales. FNQ5 resultó el compuesto más activo y selectivo. Conclusiones: este trabajo es el primero que evalúa el potencial antinflamatorio de los compuestos sintetizados. Los resultados indican que FNQ5 puede ser considerada como una molécula de uso potencial para el tratamiento de enfermedades inflamatorias que cursen con sobreproducción de óxido nítrico(AU)

A suplementação de L-arginina promove implicações ergogênicas no exercício físico? Evidências e considerações metabólicas / Does L-arginine supplementation promote ergogenic implications on exercise? Evidences and metabolic considerations

Um número crescente de pesquisas envolvendo a suplementação de aminoácidos isolados sobre o desempenho físico vem sendo realizado, mas os efeitos e os possíveis mecanismos de ação de muitos deles ainda permanecem inconclusivos. Destes, um aminoácido que vem sendo amplamente estudado, e que já faz parte da composição de inúmeros suplementos nutricionais, é a L-arginina pelo seu possível papel na estimulação da secreção do hormônio do crescimento (GH) e da insulina, além de ser um indutor da vasodilatação dependente de óxido nítrico (NO). Diversos estudos indicam que a suplementação de L-arginina pode estimular signifi cativa secreção do GH no repouso e, quando associada ao exercício, pode promover um feedback hipotalâmico negativo com conseqüente diminuição da secreção deste hormônio. A síntese protéica muscular tem sido associado à vasodilatação promovida pela L-arginina o que, em parte, pode ser considerado errôneo pelo fato desta isoladamente não aumentar a disponibilidade de substratos para recuperação muscular. Contudo, estudos que envolvem L-arginina e desempenho esportivo, bem como aqueles investigam dose e tempo de consumo desse aminoácido, são confl itantes e refl etem a escassez de trabalhos nesse contexto. A presente revisão descreve os aspectos metabólicos e possíveis efeitos ergogênicos da suplementação de L-arginina sobre o exercício físico.

A growing number of studies involving isolated aminoacids supplementation on physical performance have been achieved, but the effects and possible mechanisms of action of many of them still remain unclear. Of these, an amino acid that has been widely studied, and that is already part of the composition of many nutritional supplements, is L-arginine for its possible role in stimulating growth hormone (GH) and insulin release, beyond to be a nitric oxide dependent vasodilation inducer (NO). Several studies indicate that L-arginine supplementation can signifi cantly stimulate basal GH release and, when associated with exercise, can promote a negative hypothalamic feedback with consequent attenuation of release. Skeletal muscle protein synthesis has been associated with L-arginine-induced vasodilation which, in part, can be considered erroneous because alone it does not increase substrates availability for muscle recovery. However, studies involving L-arginine and exercise performance, as well as those investigating dose and time of consumption of this aminoacid are confl icting and refl ect the shortage of works in this context. This review describes the metabolic aspects and possible ergogenic effects of L-arginine supplementation on exercise.