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Introduction Cardiopulmonary bypass (CPB) is currently performed in infants and newborns for surgical correction of congenital heart diseases (CHDs). CPB exposes the body to extreme, nonphysiologic conditions that initiate a systemic inflammatory response accompanied by vasomotor dysfunction, and can lead to multiple organ dysfunction. Additionally, CPB has been linked to activation and injury of endothelial cells, which is associated with global inflammatory response, triggering of the coagulation system and subsequent organ dysfunction, not only in adult patients, but particularly in [...]

Resumo Fundamento As células progenitoras endoteliais (CPEs) desempenham um papel importante na manutenção da função endotelial. A síndrome metabólica (SM) está associada à disfunção das CPEs. Embora o exercício físico tenha um impacto benéfico na atividade das CPEs, seu mecanismo ainda não está completamente esclarecido. Objetivo O objetivo deste estudo é investigar os efeitos do exercício físico nas funções das CPEs e os mecanismos subjacentes em pacientes com SM. Métodos Os voluntários com SM foram divididos em grupo exercício (n=15) e grupo controle (n=15). Antes e após 8 semanas de treinamento físico, as CPEs foram isoladas do sangue periférico. Foram feitos o ensaio de unidades formadoras de colônias (UFC), o ensaio de formação de tubos, a expressão proteica do óxido nítrico sintase endotelial (eNOS), da fosfatidilinositol-3-quinase (PI3-K) e da proteína quinase B (AKT). Considerou-se um valor de probabilidade

Background: Ayanin (3,7,4'-Tri-O-methylquercetin) and 3,7-Di-O-methylquercetin (DMQ) are the main active metabolites isolated by bioguided fractionation from Croton schiedeanus, species known popularly in Colombia as “almizclillo”, which has been studied in experimental models in rats, exerting vasodilator and antihypertensive effects. Also, when the effect of these flavonoids was studied separately, important vasodilation was observed. Objective: To evaluate whether flavonoids from Croton schiedeanus have synergistic vasodilator properties when different combinations are used in isolated aorta rings. Methods: Cumulative concentrations of ayanin (10-8 M - 6x10-5 M or 0.01 µM - 60 µM) were assayed in the absence and presence of an increasing concentration of 3,7-Di-O-methylquercetin (DMQ) (10-8 - 3x10-5 M or 0.01-30 µM) in isolated rings from Wistar rats, pre-contracted with phenylephrine. The concentration-response curve with the maximal effect was compared with that obtained by Croton schiedeanus whole ethanolic extract (10-6 - 3x10-4 g/mL). Also, this combination was assayed in the presence of the nitric oxide synthetase inhibitor L-NAME (10-4 M) and the guanylate cyclase inhibitor methylene blue (10-4 M) to assess the role of the NO/cGMP pathway in this interaction. Results: Ayanin and DMQ display a dual interaction in vascular relaxant response: agonism at higher concentration ranges (10-6 - 3x10-5 M or 1-30 µM), and antagonism at lower concentration ranges (10-8 - 3x10-7 M or 0.01-0.3 µM). The efficacy at the highest concentration was greater than that obtained by the whole extract (Emax: 98.4% vs. 33.9%). This response was decreased but not reverted in the presence of L-NAME and methylene blue. Thus, the vasodilator effect of this combination does not depend entirely on the NO/cGMP cyclic pathway. Conclusion: The combined use of appropriate concentrations of these flavonoids could represent an advantage over Croton schiedeanus whole extract for vasodilator purposes. Resumen Antecedentes: Ayanina (3,7,4’-Tri-O-metilquercetina) y 3,7-Di-O-metilquercetina (DMQ) son los principales metabolitos activos aislados mediante fraccionamiento bioguiado, a partir de Croton schiedeanus, especie conocida popularmente en Colombia como “almizclillo”, la cual ha sido estudiada en modelos experimentales en ratas, ejerciendo efectos antihipertensivos y vasodilatadores. Además, al estudiar por separado el efecto de los flavonoides, se observó importante vasodilatación. Objetivo: Evaluar si los principales flavonoides de Croton schiedeanus tienen propiedades vasodilatadoras sinérgicas al utilizar diferentes combinaciones de ellos en anillos de aorta aislados. Metodología: Se analizaron concentraciones acumulativas de ayanina (10-8 M - 6x10-5 M o 0.01 µM - 60 µM) en ausencia y en presencia de concentraciones crecientes de DMQ (10-8 M - 3x10-5 M o 0.01 µM - 30 µM) en anillos aislados de ratas Wistar, pre-contraídos con fenilefrina. La curva concentración respuesta obtenida con el efecto máximo, fue comparada con la obtenida con el extracto etanólico de Croton schiedeanus (10-6 - 3x10-4 g/mL). Adicionalmente, esta combinación fue ensayada en presencia del inhibidor de óxido nítrico sintetasa L-NAME (10-4 M) y el inhibidor de guanilato ciclasa, azul de metileno (10-4 M) para evaluar el papel de la vía NO/GMPc en esta interacción. Resultados: Ayanina y DMQ muestran una interacción dual en la respuesta vascular relajante: agonismo en el rango más alto (10-6 M - 3x10-5 M o 1 µM - 30 µM), y antagonismo en el rango más bajo (10-8 M - 3x10-7 M o 0.01 µM - 0.3 µM). A altas concentraciones, la eficacia de los flavonoides fue mayor que las obtenidas por el extracto completo (Emáx: 98.4% vs 33.9%). Esta respuesta disminuyó, pero no se revirtió en presencia de L-NAME y azul de metileno. Por lo tanto, el efecto vasodilatador de esta combinación no depende enteramente de la vía NO/GMPc. Conclusión: El uso combinado de las concentraciones apropiadas de estos flavonoides podría representar una ventaja sobre el extracto de Croton schiedeanus, con propósitos vasodilatadores.

Nitric oxide (NO) plays a role in many biological mechanisms. The amounts of physiologically produced NO are associated with the concentrations of its metabolites nitrate and nitrite. This study investigated whether there is any association between the concentrations of NO metabolites nitrate, nitrite, and nitrosylated species (RXNO) in mature breast milk, saliva, and plasma in healthy lactating women (N = 30). We hypothesized that the NO metabolites concentrations in plasma are associated with those found in saliva and in breast milk. NO metabolites concentrations were measured using chemiluminensce-based assays. Nitrate concentrations in breast milk are twice as much as plasma concentrations, whereas nitrate concentrations in saliva are about eightfold higher (both P 0.05). Our results show a significant association between nitrate concentrations in plasma with those found in saliva, whereas all other relationships were not significant. In conclusion, this report shows for the first time that the physiological concentrations of NO metabolites in human breast milk are probably independent of circulating NO metabolites concentrations and may depend mostly on endogenous NO synthesis in the breast. These findings may have clinical implications for newborns and lactating women.

Dipyrone (DIP), also known as metamizole, is an over-the-counter analgesic used in Europe and Latin America. Evidence suggesting that inflammatory pain attenuation by DIP is associated with a direct impact on peripheral primary nociceptive neurons through the stimulation of nitric oxide signaling pathway. However, the molecular mechanism by which DIP activates this pathway remains unknown. The PI3Kγ/AKT signaling cascade activation is one of the well-known molecular mechanisms that promote nitric oxide production in sensory neurons. Herein, we investigated the role of the PI3Kγ/AKT signaling cascade in the context of peripheral analgesic effect of DIP. DIP was administered into PGE2 pre-sensitized paws of rats and mechanical hyperalgesia was determined using electronic von Frey test after 1 h. Nonselective or selective pharmacological inhibitors of PI3Kγ and AKT were also administered in DIP-treated rats under paws sensitized with PGE2. Intraplantar injection of DIP attenuated PGE2-induced hyperalgesia in a dose-dependent manner. Treatment with nonselective (wortmannin or LY294002) or selective (AS605240) pharmacological inhibitors of PI3Kγ reduced the peripheral antihypernociceptive effect of DIP. Consistently, AKT selective inhibitor also reversed analgesic DIP effects. Corroborating these data, we found that DIP induced AKT phosphorylation in cultured dorsal root ganglion neurons, which was prevented in the presence of PI3Kγ selective inhibitor. Taken together, these findings provide evidence that peripheral analgesic effect of DIP is dependent on the activation of PI3Kγ/AKT signaling pathway.

Made available in DSpace on 2021-06-25T12:20:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-01. Added 1 bitstream(s) on 2021-07-15T14:36:13Z : No. of bitstreams: 1 S0100-72032020000800460.pdf: 751857 bytes, checksum: 3618d3619e6e7106b8df436bc1b9992b (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Objective We examined the interaction of polymorphisms in the genes heme oxygenase-1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy. Methods The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA). Results We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness tomethyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA. Conclusion We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE. Univ Estadual Paulista, Inst Biociencias Botucatu, Dept Pharmacol, Botucatu, SP, Brazil Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Genet Ecol & Evolut, Belo Horizonte, MG, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Internal Med, Sao Paulo, SP, Brazil Univ Sao Paulo, Dept Psychiat Nursing & Human Sci, Escola Enfermagem Ribeirao Preto, Ribeirao Preto, SP, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Gynecol & Obstet, Ribeirao Preto, SP, Brazil Univ Estadual Paulista, Inst Biociencias Botucatu, Dept Pharmacol, Botucatu, SP, Brazil FAPESP: 2015/20461-8 CNPq: 2014-5/305587

SUMMARY AIM The aim of this study was to examine the roles of nitric oxide (NOx), endothelial nitric oxide synthetase (eNOS), and asymmetric dimethylarginine (ADMA), which is the major endogenous inhibitor of nitric oxide synthases (NOS), in the pathophysiology of hemorrhoidal disease. METHODS This study included 54 patients with grades 3 and 4 internal hemorrhoidal disease and 54 patients without the disease who attended the General Surgery Clinic. NOx, eNOS, and ADMA levels were measured with the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. RESULTS The patients had higher NO and eNOS levels and lower ADMA levels than the control subjects (p

Background and objective Several studies have demonstrated that mast cells are equipped with versatile tools to combat and kill bacteria. Additionally, mast cells produce and secrete a variety of mediators, which either regulate the host's immune system or directly attack bacteria. In this study, the intracellular microbicidal capacity of mast cells against Aggregatibacter actinomycetemcomitans was evaluated. Methods Murine mast cells were challenged in vitro with A actinomycetemcomitans for 3, 5, 10, and 24 hours. Subsequently, the colony-forming units were counted. Additionally, the production and release of nitric oxide and hydrogen peroxide were analyzed by DAF-FM diacetate, the Griess reaction, and the Amplex Red kit, respectively. Cell death was evaluated using FITC Annexin V and propidium iodide staining. Results Mast cells are able to efficiently eliminate periodontopathogen, with best results after 10 hours of intracellular challenge. The production/release of nitric oxide-and to a lesser extent of hydrogen peroxide-by mast cells was in agreement with its microbicidal capacity. Ninety percent of the mast cells maintained their cellular viability even after 24 hours of bacterial challenge. Conclusions This is-to the best of our knowledge-the first report to describe the intracellular microbicidal activity of mast cells against A actinomycetemcomitans, concerning the production and release of potentially bactericidal substances. Further, the low number of cell deaths confirms that the decreased number of colony-forming units was due to the higher antimicrobial activity of mast cells. The results highlight the importance of these cells in the defense mechanisms of biofilm-induced periodontal disease.

Background: Blockade of cannabinoid CB1 or vanilloid TRPV1 receptors in the ventromedial prefrontal cortex of rats respectively increases or decreases the conditioned emotional response during re-exposure to a context previously paired with footshocks. Although these mechanisms are unknown, they may involve local modulation of glutamatergic and nitrergic signaling. Aim: We investigated whether these mechanisms are involved in the reported effects of CB1 and TRPV1 modulation in the ventromedial prefrontal cortex. Methods: Freezing behavior and autonomic parameters were recorded during the conditioned response expression. Results: The CB1 receptors antagonist NIDA, or the TRPV1 agonist capsaicin (CPS) in the ventromedial prefrontal cortex increased the conditioned emotional response expression, and these effects were prevented by TRPV1 and CB1 antagonism, respectively. The increased conditioned emotional response evoked by NIDA and CPS were prevented by an NMDA antagonist or a neuronal nitric oxide synthase inhibitor. A nitric oxide scavenger or a soluble guanylate cyclase inhibitor prevented only the NIDA effects and the CPS effect was prevented by a non-selective antioxidant drug, as nitric oxide can also induce reactive oxygen species production. Conclusion: Our results suggest that CB1 and TRPV1 receptors in the ventromedial prefrontal cortex differently modulate the expression of conditioned emotional response through glutamatergic and nitrergic mechanisms, although different pathways may be involved.

Endothelial nitric oxide synthase (eNOS) malfunctioning has been proposed to contribute to the endothelial damage produced by cigarette. Besides eNOS, neuronal NOS (nNOS) is also expressed in most vascular tissues and plays an important role in the endothelium-dependent vascular relaxation. We hypothesize that nNOS may contribute to the endothelium dysfunction produced by cigarette in smokers. Vascular function was assessed in human resistance mesenteric arteries using a wire myograph, the level of protein expression by Western blot, eNOS and nNOS localization by immunofluorescence. Measurement of NO was assessed by fluorescence microscopy. Arteries of smokers showed impaired endothelium-dependent vascular relaxation in response to acetylcholine. Pharmacological nonselective blockade of NOS with l-NAME and selective nNOS blockade with inhibitor 1 reduced the relaxation of the mesenteric artery of both smokers and nonsmokers. Interestingly, the inhibitory effect of NOS inhibitors was greater in nonsmokers than in smokers. The expression of total nNOS and eNOS and the level of phosphorylation at eNOS-pSer1177 were reduced in arteries of smokers as compared with nonsmokers. No differences between groups were observed in the expression of total COX-1, COX-2, catalase and SOD-1. Immunofluorescence analysis showed the presence of nNOS in the vascular endothelium in both groups. Acetylcholine-induced NO production was impaired in arteries from smokers as compared to nonsmokers. Selective inhibition of nNOS caused a decreased in NO production, which was greater in nonsmokers than in smokers. Our data show that a decrease in nNOS expression contributes to the endothelial dysfunction caused by cigarette smoking in human.

BACKGROUND AND OBJECTIVES The literature suggests that the enzyme nitric oxide synthase (NOS) plays an important role in both periodontal disease (PD) and orofacial pain (OP), although few studies associate these two conditions simultaneously. The objective of this study was to evaluate the expression of the NOS enzyme in PD and OP, in comparison to those patients who did not present PD and/or OP. CONTENTS Seven electronic databases (Pubmed, Web of science, Scopus, Cochrane Library, BBO, LILACS, Clinical trial) were used to identify the potentially relevant studies published until April 2021. The research resulted in 1,960 studies, of which 11 were selected to be critically evaluated. Two independent reviewers selected titles and abstracts using the criteria defined in the PECO question (Population, Exposure, Comparison, Outcome). The methodological evaluation of the selected studies was carried out according to the Effective Public Health Practice Project (EPHPP). CONCLUSION: Scientific evidence demonstrated that NOS may play a key role in the pathogenesis of PD and OP, since its expression is increased in patients with these conditions. However, genetic studies on endothelial nitric oxide synthase (eNOS) gene mutations in patients with migraine and cluster headache did not indicate the expected susceptibility to pain. In addition, studies on the association of NOS expression in PD and OP, occurring simultaneously, are scarce. This review may support future research on NOS in two very common correlated diseases such as PD and OP. RESUMO JUSTIFICATIVA E OBJETIVOS A literatura sugere que a enzima óxido nítrico sintase (NOS) desempenha um papel importante tanto na doença periodontal (DP) quanto na dor orofacial (DOF), embora poucos estudos associem estas duas condições simultaneamente. O objetivo deste estudo foi analisar a expressão da NOS em pacientes com DP e DOF em comparação a controles sem estas condições. CONTEÚDO Foram consultadas as bases de dados eletrônicas (Pubmed, Web of Science, Scopus, Cochrane Library, BBO, Lilacs e Clinical Trial) para identificar os estudos potencialmente relevantes publicados até abril de 2021. As pesquisas resultaram em 1.960 estudos, dos quais 11 foram selecionados para serem avaliados criticamente. Os critérios definidos na questão PECO (População, Exposição, Comparação e Desfecho) foram usados para selecionar títulos e resumos por dois revisores independentes. A avaliação metodológica dos estudos selecionados foi realizada de acordo com a ferramenta Effective Public Health Practice Project (EPHPP). CONCLUSÃO As evidências científicas demonstraram que a NOS desempenha um importante papel na patogênese da DP e da DOF, já que sua expressão está aumentada em pacientes com estas condições. Porém, estudos genéticos sobre mutações dos genes do óxido nítrico sintase endotelial (eNOS) em pacientes com migrânea e cefaleia em salvas não evidenciaram a esperada suscetibilidade a dor. Além disso, estudos sobre a associação da expressão da NOS na DP e na DOF, ocorrendo simultaneamente, são escassos. Este estudo pode subsidiar futuras pesquisas sobre NOS na correlação de duas doenças muito frequentes como a DP e a DOF.

Brown algae of the Family Dictyotaceae produce an array of structurally diverse terpenoids, whose biomedical potential in the anti-inflammatory area has been scarcely explored. Herein, the chemical study of the alga Rugulopteryx okamurae has led to the isolation of ten new diterpenoids: rugukadiol A (1), rugukamurals A–C (2–4), and ruguloptones A–F (6–10). The structures of the new compounds were established by spectroscopic means. Compound 1 exhibits an unprecedented diterpenoid skeleton featuring a bridged tricyclic undecane system. Compounds 2–10 belong to the secospatane class of diterpenoids and differ by the oxygenated functions that they contain. In anti-inflammatory assays, the new diterpenoid 1 and the secospatanes 5 and 10 significantly inhibited the production of the inflammatory mediator NO in LPS-stimulated microglial cells Bv.2 and macrophage cells RAW 264.7. Moreover, compounds 1 and 5 were found to strongly inhibit the expression of Nos2 and the pro-inflammatory cytokine Il1b in both immune cell lines.

The optimization of conditions to promote the stemness of pluripotent cells in vitro is instrumental for their use in advanced therapies. We show here that exposure of human iPSCs and human ESCs to low concentrations of the chemical NO donor DETA/NO leads to stabilization of hypoxia-inducible factors (HIF-1α and HIF-2α) under normoxia, with this effect being dependent on diminished Pro 402 hydroxylation and decreased degradation by the proteasome. Moreover, the master genes of pluripotency, NANOG and OCT-4, were upregulated. NO also induces a shift in the metabolic profile of PSCs, with an increased expression of hypoxia response genes in glycolysis. Furthermore, a reduction in the mitochondrial membrane potential with lower oxygen consumption and increased expression of mitochondrial fusion regulators, such as DRP1, was observed. The results reported here indicate that NO mimics hypoxia response in human PSCs and enhances their stemness properties when cultured under normoxic conditions.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas Gerais O objetivo do estudo foi comparar os efeitos agudos da ingestão de uma dose de suco de beterraba com diferentes concentrações de nitrato (NO3-), na Variabilidade de Frequência Cardíaca (VFC) em mulheres hipertensas na pós menopausa. Participaram do estudo trezes mulheres hipertensas e na pós menopausa (58,1±4,62 anos e 27,4±4,25 kg/m2). As voluntárias realizaram três visitas para ingestão de diferentes sucos em ordem randomizada e cruzada: Suco de beterraba com alto teor de nitrato (High – NO3-), suco de beterraba com baixo teor de nitrato (Low – NO3-) e a bebida não calórica sabor de laranja (OFD). As voluntárias chegavam as 7h00 no laboratório e eram conduzidas até uma sala para a análise da Frequência Cardíaca (FC) de repouso na posição sentada durante 20 minutos. Posteriormente elas ingeriam uma das bebidas e permaneciam em repouso durante duas horas até o começo do exercício aeróbico em esteira ergométrica, que era realizado com intensidade a 65-70% da Frequência Cardíaca de Reserva (FCR) por 40 minutos. Após o final da sessão de exercício novamente era conduzidas até a sala e permaneciam por 90 minutos para análise da FC. A partir dos dados da FC pré e pós exercício foi calculada a VFC das três sessões nos domínios do tempo (RMSSD, SDNN, Pnn50), frequência (HF, LF, LF/HF) e não lineares (SD2, SD1, SD2/SD1). A ANOVA two way mostrou que não houve diferença em nenhum ponto dos 90 minutos nos domínios da VFC, para tempo, SDNN (p=0,24), RMSSD (p=0,59) e Pnn50 (p=0,81), para frequência, LF (p=0,54), HF (p=0,80) e LF/HF (p=0,39) e domínios não lineares, sendo, SD2 (p=0,55), SD1 (p=0,10) e SD2/SD1 (p=0,46) após a realização do exercício, quando comparadas as três sessões. Assim parece que a ingestão do suco de beterraba com alto ou baixo teor de Nitrato não alteram de maneira aguda as respostas da variabilidade da frequência cardíaca após uma sessão de exercício aeróbio em mulheres hipertensas na pós menopausa. The aim of the study was to compare the acute effects of ingesting a dose of beet juice with different concentrations of nitrate, on Heart Rate Variability (HRV) in post-menopausal hypertensive women. Thirteen hypertensive and post-menopausal women (58.1 ± 4.62 years and 27.4 ± 4.25 kg / m2) completed the protocol that consisted of three visits for ingesting different juices in a randomized and crossed order: Beet juice with high content of nitrate (High – NO3-), low nitrate beet juice (Low – NO3-) and orange flavored non-caloric drink (OFD). The volunteers arrived at 7 am in the laboratory and were taken to a room for the analysis of Heart Rate (HR) for 20 minutes. Subsequently, they ingested one of the drinks and remained at rest for two hours until the beginning of the aerobic exercise on a treadmill, which was performed with intensity at 65-70% of the Reserve Heart Rate (FCR) for 40 minutes. After the end of the exercise session, they were again taken to the room and remained for 90 minutes for HR analysis. From the HR data before and after exercise, HRV was calculated for the three sessions in the time (RMSSD, SDNN, Pnn50), frequency (HF, LF, LF / HF) and non-linear (SD2, SD1, SD2 / SD1) domains). The two-way ANOVA showed that there was no difference at any point in the 90 minutes in the HRV domains, for time, SDNN (p = 0.24), RMSSD (p = 0.59) and Pnn50 (p = 0.81), for frequency, LF (p = 0.54), HF (p = 0.80) and LF / HF (p = 0.39) and non-linear domains, being, SD2 (p = 0.55), SD1 (p = 0.10) and SD2 / SD1 (p = 0.46) after the exercise, when comparing the three sessions. Thus, it appears that the intake of beet juice with high or low Nitrate content does not acutely alter the responses of heart rate variability after an aerobic exercise session in postmenopausal hypertensive women. Dissertação (Mestrado)

Seed germination and early seedling growth are sensitive to drought stress in wheat. A factorial experiment was arranged based on a completely randomized design with three replicates to study the impacts of TiO2 nanoparticles (TiO2 NPs: 0, 500, 1000 and 2000 mg.L) and sodium nitroprusside (SNP: 0 and 100 μM), as NO donor, on seed germination and seedling growth of wheat under polyethylene glycol (PEG)-induced drought stress (0, -0.4 and -0.8 MPa). Our results revealed that PEG-stimulated drought stress significantly decreased germination percentage (GP), germination energy (GE), germination rate (GR), root length (RL), shoot length (SL), root fresh weight (RFW), shoot fresh weight (SFW) and vigor index (VI) but increased mean germination time (MGT) in wheat seeds. However, application of TiO2 NPs and SNP alone or in combination significantly enhanced GP, GE, GR, RL, SL, RFW, SFW and VI up to 23.72%, 50%, 33.74%, 85.38%, 93.28%, 73%, 91.91% and 91.04% respectively, but significantly reduced MGT up to 28.36% under severe drought stress. Our results showed that application of TiO2 NPs and SNP alone or in combination can significantly alleviate the adverse effects of PEG-stimulated drought stress on seed germination and early seedling growth of wheat. Resumo: A germinação de sementes e o crescimento inicial de plântulas são sensíveis ao estresse hídrico no trigo. O delineamento experimental foi inteiramente casualizado, com três repetições, para estudar os impactos de nanopartículas de TiO2 (NPs de TiO2: 0, 500, 1000 e 2000 mg.L) e nitroprussiato de sódio (SNP: 0 e 100 μM), como NO doador, na germinação de sementes e no crescimento de plântulas de trigo sob estresse hídrico induzido por polietilenoglicol (PEG) (0, -0,4 e -0,8 MPa). Nossos resultados revelaram que o estresse hídrico estimulado por PEG reduziu significativamente a porcentagem de germinação (GP), energia de germinação (GE), taxa de germinação (GR), comprimento de raiz (RL), comprimento da parte aérea (SL), peso fresco da raiz (RFW) peso (SFW) e índice de vigor (VI), mas aumento do tempo médio de germinação (MGT) em sementes de trigo. No entanto, a aplicação de TiO2 NPs e SNP isoladamente ou em combinação aumentou significativamente GP, GE, GR, RL, SL, RFW, SFW e VI até 23,72%, 50%, 33,74%, 85,38%, 93,28%, 73%, 91,91 % e 91,04% respectivamente, mas reduziu significativamente o TGM até 28,36% sob estresse hídrico severo. Nossos resultados mostraram que a aplicação de NPs de TiO2 e SNP isoladamente ou em combinação pode aliviar significativamente os efeitos adversos da seca causada por PEG na germinação de sementes e no crescimento inicial de plântulas de trigo.

Made available in DSpace on 2019-10-06T16:04:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-02 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) School of Medicine We investigated the involvement of nitrergic neurotransmission within the paraventricular nucleus of the hypothalamus (PVN) in modulation of local neuronal activation, autonomic and neuroendocrine responses and behavioral consequences of acute restraint stress in rats. Bilateral microinjections of the selective neuronal nitric oxide (NO) synthase (nNOS) inhibitor N w -Propyl-L-arginine (NPLA) or the NO scavenger carboxy-PTIO into the PVN reduced arterial pressure and heart rate increases, as well as the fall in cutaneous tail temperature induced by restraint stress. PVN injection of either NPLA or carboxy-PTIO also inhibited restraint-induced increases in anxiety-related behaviors in the elevated plus-maze 24 h later. Local microinjection of NPLA or carboxy-PTIO into the PVN reduced the number of c-fos-immunoreactive neurons in the dorsal parvocellular, ventromedial, medial parvocellular and lateral magnocelllular portions of the PVN in animals subjected to restraint stress. However, neither NPLA nor carboxy-PTIO into the PVN affected restraint-induced increases in plasma corticosterone concentration. The present results indicate that PVN nitrergic neurotransmission acting via nNOS activation has a facilitatory influence on autonomic responses to acute restraint and the delayed emotional consequences of restraint stress. Our results also provide evidence of a prominent role of local nitrergic neurotransmission in PVN neuronal activation during stress. Departments of Pharmacology of the School of Medicine of Ribeirão Preto University of São Paulo, 14049-900 Ribeirão Preto Department of Natural Active Principles and Toxicology School of Pharmaceutical Sciences UNESP - São Paulo State University Department of Psychiatry and Behavioral Neuroscience University of Cincinnati Department of Natural Active Principles and Toxicology School of Pharmaceutical Sciences UNESP - São Paulo State University FAPESP: 2009/05308-8 FAPESP: 2012/09425-1 FAPESP: 2013/13721-8 CNPq: 308137/2014-0

Introduction The mechanical obstruction and pulmonary vasoconstriction are major determinants of the sudden right ventricular (RV) afterload increases observed during acute pulmonary thromboembolism (APT). Vasodilators and antioxidants agents have been shown to mitigate pulmonary hypertension. We examined whether sodium nitrite and the antioxidant tempol combination could be advantageous in an APT sheep model. Methods APT was induced in anesthetized sheep by autologous blood clots (250 mg/kg) into the right atrium. Thirty minutes after APT induction, the animals received a continuous infusion of tempol (1.0 mg/kg/min), increasing sodium nitrite infusion (5, 15, and 50 μmol/kg), or a simultaneous combination of both drugs. Saline was used as a control treatment. Hemodynamic measurements were carried out every 15 min. Also, whole blood nitrite and serum 8-isoprostanes levels were measured. Results APT induced sustained pulmonary hypertension, increased dp/dtmax, and rate pressure product (RPP). Nitrite or tempol treatments attenuated these increases (P Conclusions Nitrite and tempol combination protects against APT-induced RV wall stress. The association of both drugs may offer an advantage to treat RV failure during severe APT.

Nitric oxide (NO) is an important mediator molecule in inflammatory processes, but its role in the pathophysiology of malaria is still uncertain. To investigate the NO synthesis inhibition on the oxidative changes induced by Plasmodium berghei infection in mice, malaria was induced in 150 animals, of which 75 animals were treated with the NO inhibitor L-NAME; the remaining animals were sham controls. All animals underwent euthanasia 1, 5, 10, 15, or 20 days after infection for the collection of lungs, brain, and blood. Parasitemia was determined, and the survival of the animals was evaluated. Tissue samples were assayed for nitrites and nitrates (NN), thiobarbituric acid reactive substances (TBARS), and total Trolox equivalent antioxidant capacity (TEAC). A histopathological study was performed. Mortality rates in the L-NAME group were always higher than those in the controls. In the brain, NN was lower in the L-NAME group. Parasitemia and its progression rate were greater in the control group. By the 5th day of infection, mice treated with L-NAME showed cerebral edema and interstitial pneumonia of greater intensity than controls. In conclusion, the anti-inflammatory and hemodynamic effects of NO surpass its pro-oxidant role in murine malaria. El óxido nítrico (NO) es una molécula mediadora importante en los procesos inflamatorios, pero su papel en la fisiopatología de la malaria sigue siendo incierto. Para investigar la inhibición de la síntesis de NO en los cambios oxidativos inducidos por la infección por Plasmodium berghei en ratones, la malaria se indujo en 150 animales, de los cuales 75 animales fueron tratados con el inhibidor de NO L-NAME; los animales restantes eran controles sham. Todos los animales se sometieron a eutanasia 1, 5, 10, 15 o 20 días después de la infección para la recolección de pulmones, cerebro y sangre. Se determinó la parasitemia, y se evaluó la supervivencia de los animales. Se ensayaron muestras de tejido para nitritos y nitratos (NN), sustancias reactivas de ácido tiobarbitúrico (TBARS) y capacidad antioxidante total equivalente a Trolox (TEAC). Se realizó un estudio histopatológico. Las tasas de mortalidad en el grupo L-NAME siempre fueron más altas que las de los controles. En el cerebro, NN era más baja en el grupo L-NAME. Parasitemia y su tasa de progresión fueron mayores en el grupo de control. Para el 5o día de infección, los ratones tratados con L-NAME mostraron edema cerebral y neumonía intersticial de mayor intensidad que los controles. En conclusión, los efectos antiinflamatorios y hemodinámicos de NO superan su papel pro-oxidante en la malaria murina. O óxido nítrico (NO) é uma importante molécula mediadora em processos inflamatórios, mas seu papel na fisiopatologia da malária ainda é incerto. Para investigar a inibição da síntese NO sobre as alterações oxidativas induzidas pela infecção por Plasmodium berghei em camundongos, a malária foi induzida em 150 animais, dos quais 75 animais foram tratados com o inibidor de NO L-NAME; os demais animais eram controles sham. Todos os animais foram submetidos à eutanásia 1, 5, 10, 15 ou 20 dias após a infecção para coleta de pulmões, cérebro e sangue. A parasitemia foi determinada, e a sobrevivência dos animais foi avaliada. As amostras de tecido foram avaliadas para nitritos e nitratos (NN), substâncias reativas de ácido tiobarbitúrico (TBARS) e capacidade antioxidante equivalente trolox total (TEAC). Foi realizado um estudo histopatológico. As taxas de mortalidade no grupo L-NAME sempre foram maiores do que as dos controles. No cérebro, NN era menor no grupo L-NAME. A parasitemia e sua taxa de progressão foram maiores no grupo controle. No 5th dia de infecção, os camundongos tratados com L-NAME apresentaram edema cerebral e pneumonia intersticial de maior intensidade do que os controles. Em conclusão, os efeitos anti-inflamatórios e hemodinâmicos de NO superam seu papel pró-oxidante na malária murina.

The contractions of Chelonoidis carbonaria aortic rings induced by electrical field stimulation (EFS) are not inhibited by blockade of the voltage-gated sodium channels by tetrodotoxin but almost abolished by the α1/α2-adrenoceptor antagonist phentolamine. The objective of this study was to identify the mediator(s) responsible for the EFS-induced contractions of Chelonoidis carbonaria aortic rings. Each ring was suspended between two wire hooks and mounted in isolated 10 ml organ chambers filled with oxygenated and heated Krebs-Henseleit's solution. Dopamine, noradrenaline and adrenaline concentrations were analysed by liquid chromatography coupled to tandem mass spectrometry. The contractions caused by dopamine and EFS were done in absence and presence of the nitric oxide (NO) synthesis inhibitor L-NAME, the NO-sensitive guanylyl cyclase inhibitor ODQ, the D1-like receptor antagonist SCH-23390, the D2-like receptor antagonists risperidone, quetiapine, haloperidol, and the tyrosine hydroxylase inhibitors salsolinol and 3-iodo-L-tyrosine. Basal concentrations of dopamine, noradrenaline and adrenaline were detected in Krebs-Henseleit solution containing the aortic rings. The catecholamine concentrations were significantly reduced in endothelium-denuded aortic rings. L-NAME and ODQ significantly potentiated the dopamine-induced contractions. The D2-like receptor antagonists inhibited the EFS-induced contractions of the aortic rings treated with L-NAME, whereas SCH 23390 had no effect. Similar results were observed in the contractions induced by dopamine in L-NAME treated aortic rings. These results indicate that catecholamines released by endothelium regulate the EFS-induced contractions. This may constitute a suitable mechanism by which reptilia modulate specific organ blood flow distribution. This paper has an associated First Person interview with the first author of the article., Summary: Chelonoidis carbonaria aortic rings release endothelium-derived catecholamines that modulate vascular smooth muscle reactivity.

Introduction: Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia that leads to diabetic nephropathy (DN). We showed that P2X7, a purinergic receptor, was highly expressed in DM; however, when oxidative stress was controlled, renal NO recovered, and the activation of this receptor remained significantly reduced. The aim of this study was to assess the influence of NO on the P2X7 and apoptosis in mouse immortalized mesangial cells (MiMC) cultured in high glucose (HG) medium. Methods: MiMCs were cultured with DMEM and exposed to normal glucose (NG), mannitol (MA), or HG. Cell viability was assessed by an automated counter. Supernatants were collected for NO quantification, and proteins were extracted for analysis of NO synthases (iNOS and eNOS), caspase-3, and P2X7. Results: Cell viability remained above 90% in all groups. There was a significant increase in the proliferation of cells in HG compared to MA and NG. NO, iNOS, caspase-3, and P2X7 were significantly increased in HG compared to NG and MA, with no changes in eNOS. We observed that there was a strong and significant correlation between P2X7 and NO. Discussion: The main finding was that the production of NO by iNOS was positively correlated with the increase of P2X7 in MCs under HG conditions, showing that there is a common stimulus between them and that NO interacts with the P2X7 pathway, contributing to apoptosis in experimental DM. These findings could be relevant to studies of therapeutic targets for the prevention and/or treatment of hyperglycemia-induced kidney damage to delay DN progression. Resumo Introdução: Diabetes mellitus (DM) é uma doença crônica caracterizada por hiperglicemia levando à nefropatia diabética (ND). Mostramos que P2X7, um receptor purinérgico, foi altamente expresso na DM; entretanto, quando o estresse oxidativo foi controlado, o NO renal recuperou-se, e a ativação deste receptor permaneceu significativamente reduzida. Este estudo objetivou avaliar a influência do NO no P2X7 e a apoptose em células mesangiais imortalizadas de camundongos (CMiC) cultivadas em meio de glicose elevada (GE). Métodos: CMiCs foram cultivadas em meio DMEM e expostas à glicose normal (GN), manitol (MA), ou GE. A viabilidade celular foi avaliada por contador automático. Sobrenadantes foram coletados para quantificação de NO, e foram extraídas proteínas para análise de NO sintases (iNOS e eNOS), caspase-3, e P2X7. Resultados: A viabilidade celular permaneceu acima de 90% em todos os grupos. Houve aumento significativo na proliferação de células na GE comparado com MA e GN. NO, iNOS, caspase-3 e P2X7 foram significativamente aumentados na GE comparados com GN e MA, sem alterações na eNOS. Observamos que houve correlação forte e significativa entre P2X7 e NO. Discussão: O principal achado foi que a produção de NO pela iNOS foi positivamente correlacionada com aumento de P2X7 em CMs sob condições de GE, mostrando que existe um estímulo comum entre eles e que o NO interage com a via do P2X7, contribuindo para apoptose na DM experimental. Estes achados podem ser relevantes para estudos de alvos terapêuticos para a prevenção e/ou tratamento de danos renais induzidos por hiperglicemia para retardar a progressão da ND.

Inflammatory bowel diseases (IBDs) are chronic diseases of the gastrointestinal tract that include ulcerative colitis and Crohn's disease and affect enteric neurons. Research has shown that Brilliant Blue G (BBG), a P2X7 receptor antagonist, restores enteric neurons following ischemia and reperfusion. This study aimed to evaluate the effect of BBG on myenteric neurons of the distal colon in an experimental rat model of ulcerative colitis. Colitis was induced by injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the large intestine. BBG was administered 1 h after colitis induction and for five consecutive days thereafter. Distal colons were collected 24 h or 7 days after TNBS injection. The animals were divided into 24-h and 7-day sham (vehicle injection rather than colitis induction), 24-h colitis, 24-h BBG, 7-day colitis and 7-day BBG groups. The disease activity index (DAI), neuronal density and profile of neuronal nitric oxide synthase (nNOS)-, choline acetyltransferase (ChAT)- and P2X7 receptor-immunoreactive enteric neurons were analyzed, and histological analysis was performed. The results showed recovery of the DAI and histological tissue integrity in the BBG groups compared to those in the colitis groups. In addition, the numbers of neurons positive for nNOS, ChAT and the P2X7 receptor per area were decreased in the colitis groups, and these measures were recovered in the BBG groups. Neuronal size was increased in the colitis groups and restored in the BBG groups. In conclusion, BBG is effective in improving experimental ulcerative colitis, and the P2X7 receptor may be a therapeutic target.

Carbon monoxide (CO) and nitric oxide (NO) modulate inflammatory nociception and anxiety. We evaluate whether treatments with a heme oxygenase-1 (HO-1) inducer (CoPP) or a carbon monoxide-releasing molecule (CORM-2) are capable of inhibiting inflammatory pain aversiveness in wild type (WT) and inducible nitric oxide synthase-knock out (NOS2-KO) mice with persistent inflammation and its relationship with μ- (MOR) and δ- (DOR) opioid receptors. WT and NOS2-KO male mice with complete Freund's adjuvant (CFA) injected into the hind paw were evaluated in the von Frey and the escape-avoidance paradigm (PEAP) tests, at 10 days, before and after the treatment with CORM-2 (5 mg/kg) or CoPP (2.5 mg/kg). WT mice groups treated with CORM-2 or CoPP also received naloxone (NLX, a non-specific opioid receptor antagonist). The HO-1, neuronal nitric oxide synthase, NOS2, MOR, and DOR expression in the dorsal hippocampus were evaluated by western blot. CFA reduced mechanical threshold in WT and NOS2-KO mice but only increased the percentage of time in the light compartment in the PEAP in WT mice. CORM-2 and CoPP inhibited these effects in both strains. Pre-treatment with NLX reverses the anti-allodynic and anti-aversive effects of CORM-2 or CoPP in WT mice. CORM-2 and CoPP increases the protein levels of HO-1, MOR and DOR in the dorsal hippocampus of WT mice but not in NOS2-KO animals. Results showed that HO CO pathway activation promotes anti-allodynic effects and reduced pain aversiveness caused by peripheral inflammation by increasing the expression of MOR and DOR activated by HO-1 in the dorsal hippocampus.

Thyroid cancer is the most common endocrine cancer in the world. Noting that the NOS3 gene polymorphism interferes with nitric oxide production, this study aims to identify and analyze the NOS3 gene polymorphism in the intron 4 region in patients with papillary thyroid cancer. A case-control study was conducted with 31 papillary thyroid cancer patients of both genders who underwent thyroidectomy and treatment with sodium iodide radiopharmaceutical (131I) compared with 81 control patients. Through papillary thyroid cancer, the results were observed, compiled, and analyzed using SPSS version 25.0. The significance level of 5% was adopted. Genotypic frequencies of healthy subjects were in the Hardy-Weinberg equilibrium ( P = 0.503). There was a significant genotypic difference between papillary thyroid cancer and healthy individuals ( P

© 2020 by the authors., Oxidative stress plays an important role in the pathogenesis of ocular diseases, including hypertensive eye diseases. The beneficial effects of olive oil on cardiovascular diseases might rely on minor constituents. Currently, very little is known about the chemical composition and/or therapeutic effects of the cultivated olive tree’s counterpart, wild olive (also known in Spain as acebuche—ACE). Here, we aimed to analyze the antioxidant and retinoprotective effects of ACE oil on the eye of hypertensive mice made hypertensive via administration of NG-nitro-L-arginine-methyl-ester (L-NAME), which were subjected to a dietary supplementation with either ACE oil or extra virgin olive oil (EVOO) for comparison purposes. Deep analyses of major and minor compounds present in both oils was accompanied by blood pressure monitoring, morphometric analyses, as well as different determinations of oxidative stress-related parameters in retinal layers. Aside from its antihypertensive effect, an ACE oil-enriched diet reduced NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activity/gene/protein expression (with a major implication of NADPH oxidase (NOX)2 isoform) in the retinas of hypertensive mice. Supplementation with ACE oil in hypertensive animals also improved alterations in nitric oxide bioavailability and in antioxidant enzyme profile. Interestingly, our findings show that the use of ACE oil resulted in better outcomes, compared with reference EVOO, against hypertension-related oxidative retinal damage., This study was supported by Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (2017/440; 2020/275; CTS-584), Ministerio de Ciencia e Innovación, Gobierno de España (Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020, Programa Estatal de I+D+i Orientada a los Retos de la Sociedad; PID2019-109002RB-I00), and VI PPIT Universidad de Sevilla (IV.7 Ayuda Suplementaria a Grupos de Investigación por captación de fondos en las convocatorias de proyectos de investigación del Plan Estatal; 2020/1163). AS is recipient of an FPU predoctoral fellowship from Ministerio de Ciencia, Innovación y Universidades (FPU17/03465). CR-G was supported by Ministerio de Ciencia e Innovación, Ayudas para la Promoción de Empleo Joven e Implantación de la Garantía Juvenil en I+D+i 2017-2020 (PEJ2018-004474-A).

Introdução: O controle da pressão arterial se dá através da interação entre o sistema nervoso autônomo e substâncias secretadas por diferentes tipos de células, entre elas as endoteliais, fazendo com que alterações em algum desses mecanismos acarretem o desenvolvimento da hipertensão arterial. A prática de exercícios físicos se mostra como um tratamento não-farmacológico capaz de reduzir significativamente tanto a pressão arterial sistólica como a diastólica, atenuar a reatividade pressórica e aumentar a biodisponibilidade de óxido nítrico. Objetivo: A presente revisão crítica tem como objetivo realizar um levantamento bibliográfico dos principais estudos sobre exercícios intervalados, reatividade pressórica e óxido nítrico. Metodologia: Foram selecionados artigos com tais temáticas e depois classificados em categorias com as definições dos conceitos. Conclusão: Portanto, sugere-se o treino intervalado para promover alterações na reatividade vascular e nas concentrações de óxido nítrico dependerá da intensidade e volume.

Introduction This article discusses the production of nitric oxide under the influence of sport-specific physical training, measured by the salivary nitrite of Jiu-Jitsu athletes. Objectives To verify the potential of the sport to produce optimal levels of nitric oxide stimulated by exertion, and to quantify training-related nitric oxide concentrations. Method The study participants were 14 volunteer athletes from the Tatame project (extension project), who were monitored for nine months in their training routine, providing samples of unstimulated saliva. Samples were collected each month, in three periods of the day: in the morning upon waking, immediately before training, and immediately after training. Salivary nitrite was quantified by the colorimetric Griess assay. Training heart rates were also monitored in order to establish training intensity. Results Mean monthly salivary nitrite levels showed a significant correlation with mean monthly heart rates, suggesting that salivary nitrite responds to training. However, salivary nitrite concentrations measured immediately after training were always lower than in the pre-training period. Conclusion The post-training reduction in concentrations was due to the nature of the sport studied, since because it involves a fight, the intense sympathetic stimulation inhibited salivary gland activity and irrigation, preventing salivary nitrite from producing an increase in circulating nitric oxide. Level of evidence IV; Case series. RESUMO Introdução Este artigo discute a produção de óxido nítrico sob interferência do treinamento físico esportivo, medida pelo nitrito salivar em atletas de Jiu-Jitsu. Objetivos Verificar as potencialidades da modalidade na produção de níveis ideais de óxido nítrico estimulado pelo esforço e quantificar as concentrações de óxido nítrico relacionadas com o treinamento. Métodos O estudo teve a participação de 14 atletas voluntários do Projeto Tatame (projeto de extensão), que foram acompanhados por nove meses em sua rotina de treinamento e forneceram amostras de saliva não estimulada. Foram coletadas amostras a cada mês, em três períodos do dia: pela manhã ao acordar, imediatamente antes do treino e imediatamente após o treino. O nitrito salivar foi quantificado pelo método colorimétrico de Griess. Também foram monitoradas as frequências cardíacas de treinamento a fim de se estabelecer a intensidade do treinamento realizado. Resultados As médias mensais de nitrito salivar demonstraram correlação significativa com as médias mensais de frequência cardíaca, dando indícios de que o nitrito salivar responde ao treinamento. Contudo, as concentrações de nitrito salivar medidas imediatamente após o treinamento sempre eram menores com relação ao período anterior do treino. Conclusão A redução da concentração depois do treinamento deveu-se à natureza da modalidade estudada, visto que, por ser uma luta, a forte carga de estimulação simpática inibiu a atividade das glândulas salivares, bem como sua irrigação, impedindo que o nitrito salivar produzisse aumento do óxido nítrico circulante. Nível de evidência IV; Série de casos. RESUMEN Introducción Este artículo analiza la producción de óxido nítrico bajo la influencia del entrenamiento físico deportivo, medida por el nitrito salival de atletas de Jiu-Jitsu. Objetivos Verificar el potencial de la modalidad en la producción de niveles ideales de óxido nítrico estimulado por el esfuerzo y cuantificar las concentraciones de óxido nítrico relacionadas con el entrenamiento. Métodos El estudio contó con la participación de 14 atletas voluntarios participantes del Proyecto Tatame (proyecto de extensión) a quienes se les dio seguimiento durante nueve meses en su rutina de entrenamiento y proporcionaron muestras de saliva no estimulada. Se recolectaron muestras cada mes, en tres períodos del día: en la mañana al despertar, inmediatamente antes del entrenamiento e inmediatamente después del entrenamiento. El nitrito salival se cuantific ó por el método colorimétrico de Griess. Las frecuencias cardíacas de entrenamiento se monitorearon para establecer la intensidad del entrenamiento realizado. Resultados Los promedios mensuales de nitrito salival mostraron una correlación significativa con los promedios mensuales de frecuencia cardíaca, lo que indica que el nitrito salival responde al entrenamiento. Sin embargo, las concentraciones de nitrito salival medidas inmediatamente después del entrenamiento siempre fueron más bajas en comparación con el período anterior al entrenamiento. Conclusión La reducción de la concentración después del entrenamiento se debió a la naturaleza de la modalidad estudiada, ya que, por ser una lucha, la fuerte carga de estimulación simpática inhibió la actividad de las glándulas salivales, así como su irrigación, evitando que el nitrito salival produjera aumento de óxido nítrico circulante. Nivel de evidencia IV; Serie de casos.

Histoplasma capsulatum is the agent of histoplasmosis, one of the most frequent mycoses in the world. The infection initiates with fungal spore inhalation, transformation into yeasts in the lungs and establishment of a granulomatous disease, which is characterized by a Th1 response. The production of Th1 signature cytokines, such as IFN-&gamma, is crucial for yeast clearance from the lungs, and to prevent dissemination. Recently, it was demonstrated that IL-17, a Th17 signature cytokine, is also important for fungal control, particularly in the absence of Th1 response. IL-22 is another cytokine with multiple functions on host response and disease progression. However, little is known about the role of IL-22 during histoplasmosis. In this study, we demonstrated that absence of IL-22 affected the clearance of yeasts from the lungs and increased the spreading to the spleen. In addition, IL-22 deficient mice (Il22&minus, /&minus, ) succumbed to infection, which correlated with reductions in the numbers of CD4+ IFN-&gamma, + T cells, reduced IFN-&gamma, levels, and diminished nitric oxide synthase type 2 (NOS2) expression in the lungs. Importantly, treatment with rIFN-&gamma, mitigated the susceptibility of Il22&minus, mice to H. capsulatum infection. These data indicate that IL-22 is crucial for IFN-&gamma, /NO production and resistance to experimental histoplasmosis.

Endurance can be defined as the capacity to maintain one’s velocity or power output for the longest possible time. Maintaining such activity can lead to the onset of fatigue. Dietary nitrate supplementation produces an ergogenic effect due to the improvement of mitochondrial oxygen efficiency through a reduction in the oxygen cost of exercise that increases vasodilation and blood flow to the skeletal muscle in recreationally active subjects. However, the effects of dietary nitrate supplementation on well-trained endurance athletes remain unclear; such supplementation could affect more performance areas. In the present study, a systematic review of the literature was conducted to clarify the use and effects of nitrate as a dietary supplement in endurance athletes trained in cyclic sports (repetitive movement sports). A systematic search was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines in the databases of SCOPUS, Web of Science (WOS), Medline (PubMed), and Sport Discus from 1 January 2010 to 30 November 2019. Twenty-seven studies were included in the study. The methodological quality of the articles was assessed using the McMaster Critical Review Form. Statistically significant ergogenic results were obtained in 8 (29.63%) of the 27 studies investigated, with significant results obtained for cardiorespiratory parameters and performance measures. Improvement in exercise tolerance was obtained, which could help with exhaustion over time, while the improvement in exercise economics was not as clear. Additionally, the dose necessary for this ergogenic effect seems to have a direct relationship with the physical condition of the athlete. The acute dose is around 6–12.4 mmol/day of nitrate administered 2–3 h before the activity, with the same amount given as a chronic dose over 6–15 days. Further studies are required to understand the factors that affect the potential ergogenic impacts of nitrate on athletic performance among endurance athletes Sin financiación 5.717 JCR (2020) Q1, 17/89 Nutrition & Dietetics 1.418 SJR (2020) Q1, 18/332 Food Science No data IDR 2019 UEM

Pulmonary hypertension (PH) is a major cause of morbi-mortality among patients with congenital heart disease (CHD) and also a potentially severe complication after surgical repair. Oral citrulline, a precursor to NO synthesis, is safe and efficacious for decreasing the risk of postoperative PH. Objective: The aim of the present study was to investigate in pediatric patients the changes of plasma citrulline, arginine, homocysteine and nitric oxide (NO) metabolites and pulmonary artery pressures (PAP) pre-post cardiac surgery in order to describe our population status with regard to the risk of pulmonary hypertension and look for potential biomarkers for early detection and treatment. Main results/Discussion: 16 Argentine pediatric patients with CHD undergoing cardiopulmonary bypass were randomized in two groups: (A) with and (B) without perioperative citrulline supplementation. We found that plasma citrulline median levels before surgery were lower in both groups respect to referential values, probably due to the poor nutritional status of our patients; only group A surpassed post-surgery the minimum recommended level to avoid PH. Furthermore, none of the patients in group A showed mean PAP higher than 20 mmHg, whereas in group B, 67% of the measurements were ≥ than the reference level. Conclusions: We reaffirm that citrulline supplementation it is effective in reducing postoperative pulmonary hypertension and biomarkers could evidence patient status as a translational medicine application. La hipertensión pulmonar (HP) es una causa importante de morbimortalidad entre pacientes con cardiopatía congénita (CHD) y también una complicación potencialmente grave después de la reparación quirúrgica. La citrulina oral, precursora de la síntesis de óxido nítrico, es segura y eficaz para disminuir el riesgo postoperatorio de HP. Objetivo: El presente estudio tuvo como objetivo investigar en pacientes pediátricos los cambios plasmáticos de los metabolitos citrulina, arginina, homocisteína y óxido nítrico y la presión arterial pulmonar (PAP) antes y después de la cirugía cardíaca para describir el estado de nuestra población con respecto al riesgo de HP y buscar posibles biomarcadores para su detección y tratamiento temprano. Resultados principales / Discusión: 16 pacientes pediátricos argentinos con CHD sometidos a bypass cardiopulmonar fueron aleatorizados en dos grupos: (A) con y (B) sin suplementación perioperatoria de citrulina. Encontramos que los niveles medios de citrulina en plasma antes de la cirugía fueron más bajos en ambos grupos con respecto a los valores referenciales, probablemente debido a un estado nutricional deficiente de nuestros pacientes; solo el grupo A superó el nivel mínimo recomendado para evitar la HP. Además, ninguno de los pacientes en el grupo A mostró una PAP media superior a 20mmHg, mientras que en el grupo B, el 67% de las mediciones fue mayor que el nivel de referencia. Conclusiones: Reafirmamos que la suplementación con citrulina es efectiva para reducir la HP postoperatoria y que los biomarcadores podrían evidenciar el estado del paciente como una aplicación de medicina traslacional. A hipertensão pulmonar (HP) é uma das principais causas de morbimortalidade entre pacientes com cardiopatia congênita (DCC) e também uma complicação potencialmente grave após o reparo cirúrgico. A citrulina oral, precursora da síntese do NO, é segura e eficaz para diminuir o risco de HP pós-operatória. Objetivo: O objetivo do presente estudo foi investigar em pacientes pediátricos as alterações dos metabólitos plasmáticos da citrulina, arginina, homocisteína e óxido nítrico (NO) e pressões da artéria pulmonar (PAP) prépós-cirurgia cardíaca, a fim de descrever nosso status populacional com com relação ao risco de hipertensão pulmonar e procure potenciais biomarcadores para detecção e tratamento precoces. Principais resultados / Discussão: 16 pacientes pediátricos argentinos com DCC submetidos à circulação extracorpórea foram randomizados em dois grupos: (A) com e (B) sem suplementação peri-operatória de citrulina. Descobrimos que os níveis médios de citrulina plasmática antes da cirurgia eram menores nos dois grupos em relação aos valores referenciais, provavelmente devido ao mau estado nutricional de nossos pacientes; somente o grupo A superou no pós-operatório o nível mínimo recomendado para evitar HP. Além disso, nenhum dos pacientes do grupo A apresentou PAP média superior a 20 mmHg, enquanto no grupo B, 67% das medidas foram ≥ acima do nível de referência. Conclusões: Reafirmamos que a suplementação com citrulina é eficaz na redução da hipertensão pulmonar no pósoperatório e os biomarcadores podem evidenciar o status do paciente como aplicação de medicamento translacional. publishedVersion Fil: Silvera Ruiz, Silene. Universidad Nacional de Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI); Argentina. Fil: Silvera Ruiz, Silene. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET). Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI); Argentina. Fil: Grosso, Carola L. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina. Fil: Grosso, Carola L. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas (CEMECO); Argentina. Fil: Grosso, Carola L. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Centro de Estudio de las Metabolopatías Congénitas (CEMECO); Argentina. Fil: Tablada, Elena Margot. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina. Fil: Cabrera, Marcelo. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad. Servicio de Cardiología; Argentina. Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina. Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas (CEMECO); Argentina. Fil: Dodelson de Kremer, Raquel. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Centro de Estudio de las Metabolopatías Congénitas (CEMECO); Argentina. Fil: Juaneda, Ernesto. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad. Servicio de Cardiología; Argentina. Fil: Laura E Laróvere. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina. Fil: Laura E Laróvere. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas (CEMECO); Argentina. Fil: Laura E Laróvere. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Centro de Estudio de las Metabolopatías Congénitas (CEMECO); Argentina. Fil: Laura E Laróvere. Consejo Nacional de Investigación Científica y Técnica (CONICET); Argentina.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior O endotélio é um tipo de tecido epitelial, formado por uma única camada de células, que recobre internamente os vasos sanguíneos e é essencial para a manutenção da homeostase vascular, garantida pela produção de biomoléculas vasoativas. Um desequilíbrio na biodisponibilidade dessas biomoléculas pode desencadear um estado patológico, como a disfunção endotelial (DE), que se caracteriza, principalmente, pela redução na disponibilidade do óxido nítrico (NO) e por um aumento na produção de espécies reativas de oxigênio (EROs). Dada a importância do entendimento da disfunção endotelial para o progresso de patologias como a aterosclerose, por exemplo, faz-se necessário o desenvolvimento de modelos experimentais que simulem tal condição. Assim, esse estudo foi realizado visando desenvolver e caracterizar um modelo celular in vitro de DE pela inibição da síntese de NO. Inicialmente, realizou-se o tratamento das células endoteliais derivadas do timo (linhagem tEnd.1) com o inibidor da síntese de NO (L-NAME) nas concentrações 1µM, 10 µM, 100 µM e 1mM por 12, 24, 48, 72, 96 e 120 horas, com e sem retratamento a cada 24 horas. Posteriormente, determinou-se as melhores condições de tratamento para indução de um estado de DE nas células, a partir da avaliação da viabilidade celular e da concentração de nitrito. Os tratamentos com 10 µM e 100 µM de L-NAME, nos tempos de 72 horas sem retratamento e de 96 horas com retratamento foram selecionados. Em seguida, realizou-se a qPCR para os genes p22phox, p47phox e eNOS. Os resultados foram significativos para o p22phox, em que os níveis relativos de mRNA do gene foram reduzidos em 65% em resposta ao tratamento com L-NAME 100 µM por 96 horas com retratamento. A análise da expressão proteica da eNOS por Western blotting não foi bem-sucedida. Por fim, os resultados de avaliação de peroxidação lipídica pela técnica de Buege e Aust não foram estatisticamente significativos. Em conjunto, os resultados apontam que o tratamento com L-NAME 100 µM por 96 horas com retratamento foi capaz de induzir a DE, diminuindo a disponibilidade de NO, a qual foi verificada tanto pela redução na concentração de nitrito quanto pela redução na expressão de p22phox. Entretanto, estudos adicionais, sobretudo visando aprofundar o papel das EROs nas células submetidas ao tratamento com L-NAME, são necessários para o aprimoramento e caracterização do modelo experimental proposto. Vascular endothelium is a type of epithelial tissue, formed by a monolayer of cells, which internally covers blood vessels and is essential for the maintenance of vascular homeostasis, guaranteed by the production of vasoactive biomolecules. An imbalance in the bioavailability of these biomolecules may trigger a pathological state, such as endothelial dysfunction (ED), which is mainly characterized by a reduction in the availability of nitric oxide (NO) and an increase in the production of reactive oxygen species (ROS). Considering the importance of endothelial dysfunction for the progress of pathologies such as atherosclerosis, for example, it is necessary to develop experimental models that simulate such a condition. This study was then carried out to develop and characterize an in vitro cellular model of ED by inhibiting NO synthesis. Initially, the thymus-derived endothelial cells (tEnd.1 line) were treated with the NO synthesis inhibitor (L-NAME) at 1μM, 10 μM, 100 μM and 1mM for 12, 24, 48, 72 , 96 and 120 hours, with and without retreatment every 24 hours. Subsequently, the best treatment conditions for inducing an ED state in the cells were determined based on the evaluation of cell viability and nitrite concentration. Treatments with 10 μM and 100 μM of L-NAME for 72 hours without retreatment and 96 hours with retreatment were selected. Real-time PCR was performed for p22phox, p47phox and eNOS genes. Results were significant for p22phox, in which the relative levels of gene mRNA were reduced by 65% in response to 100 μM L-NAME for 96 hours with retreatment. Western blotting analysis of eNOS protein expression was not successful. Finally, results of the evaluation of lipid peroxidation using the Buege and Aust technique were not statistically significant. Together, the results show that treatment with 100 μM L-NAME for 96 hours with retreatment was able to induce ED, decreasing the availability of NO, which was verified by the reduction in the concentration of nitrite and by the reduction in the expression of p22phox. However, additional studies aiming to determine the role of ROS in cells submitted to treatment with L-NAME are necessary for the improvement and characterization of the proposed experimental model. Dissertação (Mestrado) 2022-02-21

Fil: Mensegue, Melisa F. University of Buenos Aires. Institute of Medical Research A. Lanari; Argentina Fil: Mensegue, Melisa F. National Scientific and Technical Research Council. Institute of Medical Research (IDIM). Department of Molecular Genetics and Biology of Complex Diseases; Argentina Fil: Burgueño, Adriana. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Burgueño, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Tellechea, Mariana L. University of Buenos Aires. Institute of Medical Research A. Lanari; Argentina Fil: Tellechea, Mariana L. National Scientific and Technical Research Council. Institute of Medical Research (IDIM). Department of Molecular Genetics and Biology of Complex Diseases; Argentina Fil: Tellechea, Mariana L. Hospital de Niños Ricardo Gutiérrez. Centro de Investigaciones Endocrinológicas Dr. César Bergadá. División de Endocrinología; Argentina Abstract: Essential hypertension is considered to be a result of the interaction between genetic and environmental factors, including perinatal factors. Different advantageous perinatal factors proved to have beneficial long-lasting effects against an abnormal genetic background. Taurine is a ubiquitous sulphur-containing amino acid present in foods such as seafood. The antihypertensive effects of taurine have been reported in experimental studies and in human hypertension. We aimed to investigate the effects of perinatal treatment with taurine in spontaneously hypertensive rats (SHR), a known model of genetic hypertension. Female SHR were administered with taurine (3 g/L) during gestation and lactation (SHR-TAU). Untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. Long-lasting effects in offspring were investigated. Addition of taurine to the mother's drinking water reduced blood pressure in adult offspring. No differences were observed in cardiac hypertrophy. Findings on morphometric evaluations suggest that perinatal treatment with taurine would be partially effective in improving structural alterations of the aorta. Modifications in gene expression of Bcl-2 family members and upregulation of endothelial nitric oxide synthase in the aorta of 22-week-old male offspring were found. No differences were observed on relative telomere length in different cardiovascular tissues between SHR and SHR-TAU. Altogether results suggest that taurine programming, albeit sex specific, is associated with gene expression changes which ultimately may lead to improvement of aortic remodelling and enhanced endothelial function because of augmented nitric oxide (NO) production.

BACKGROUND The P2X7 receptor is expressed by enteric neurons and enteric glial cells. Studies have demonstrated that administration of a P2X7 receptor antagonist, brilliant blue G (BBG), prevents neuronal loss. AIM To report the effects of BBG in ileum enteric neurons immunoreactive (ir) following experimental ulcerative colitis in Rattus norvegicus albinus. METHODS 2,4,6-trinitrobenzene sulfonic acid (TNBS group, n = 5) was injected into the distal colon. BBG (50 mg/kg, BBG group, n = 5) or vehicle (sham group, n = 5) was given subcutaneously 1 h after TNBS. The animals were euthanized after 24 h, and the ileum was removed. Immunohistochemistry was performed on the myenteric plexus to evaluate immunoreactivity for P2X7 receptor, neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), HuC/D and glial fibrillary acidic protein. RESULTS The numbers of nNOS-, ChAT-, HuC/D-ir neurons and glial fibrillary acidic protein-ir glial cells were decreased in the TNBS group and recovered in the BBG group. The neuronal profile area (μm2) demonstrated that nNOS-ir neurons decreased in the TNBS group and recovered in the BBG group. There were no differences in the profile areas of ChAT- and HuC/D-ir neurons. CONCLUSION Our data conclude that ileum myenteric neurons and glial cells were affected by ulcerative colitis and that treatment with BBG had a neuroprotective effect. Thus, these results demonstrate that the P2X7 receptor may be an important target in therapeutic strategies.

Previously, we demonstrated the anti-inflammatory properties of vestitol in a neutrophil model. Here, we show the effects of vestitol on macrophage activation and function. Vestitol was obtained from Brazilian red propolis after bioguided fractionation and tested at different concentrations in LPS-activated RAW 264.7 murine macrophages for nitric oxide (NO) production and cell viability. The levels of TNF-α, IL1-β, TGF-β, IL-4, IL-6, IL-10, IL-12, GM-CSF, IFN-ɣ and gene expression related to cytokines, NO, PI3K-AKT and signal transduction pathways were assayed by ELISA and RT-qPCR, respectively. Differences were determined by one-way ANOVA followed by Tukey-Kramer. Vestitol inhibited NO production by 83% at 0.55 μM without affecting cell viability when compared to the vehicle control (P < 0.05). Treatment with vestitol reduced GM-CSF, IL-6, TNF-α, IL-4 and TGF-β levels and increased IL-10 release (P < 0.05). Vestitol affected the expression of genes related to NF-κB pathway, NO synthase, and inhibition of leukocyte transmigration, namely: Ccs, Ccng1, Calm1, Tnfsf15, Il11, Gata3, Gadd45b, Cdkn1b, Csf1, Ccl5, Birc3 (negatively regulated), and Igf1 (positively regulated). Vestitol diminished the activation of NF-κB and Erk 1/2 pathways and induced macrophages into M2-like polarization. The modulatory effects of vestitol are due to inhibition of NF-κB and Erk 1/2 signaling pathways, which are associated with the production of pro-inflammatory factors.

Producción Científica, Nitric oxide related ergogenic aids such as arginine (Arg) have shown to impact positively on sport performance through several physiological and metabolic mechanisms. However, research results have shown to be controversial. The great differences regarding required metabolic pathways and physiological demands between aerobic and anaerobic sport disciplines could be the reasons. The aim of this systematic review and meta-analysis was to evaluate the effects of Arg supplementation on aerobic (≤VO2max) and anaerobic (>VO2max) performance. Likewise, to show the effective dose and timing of this supplementation. A structured search was carried out in accordance with PRISMA® (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and PICOS guidelines in PubMed/MEDLINE, Web of Science (WOS), and Scopus databases from inception to January 2020. Eighteen studies were included which compare Arg supplementation with placebo in an identical situation and testing its effects on aerobic and anaerobic performance tests. Trials analyzing supplementation with other supplements were removed and there was not athlete’s level, gender, ethnicity, or age filters. The performed meta-analysis included 15 studies and random effects model and pooled standardized mean differences (SMD) were used according to Hedges’ g. Results revealed that Arg supplementation could improve aerobic (SMD, 0.84; 95% CI, 0.12 to 1.56; magnitude of SMD (MSMD), large; I2, 89%; p = 0.02) and anaerobic (SMD, 0.24; 95% CI, 0.05 to 0.43; MSMD, small; I2, 0%; p = 0.01) performance tests. In conclusion, acute Arg supplementation protocols to improve aerobic and anaerobic performance should be adjusted to 0.15 g/kg of body weight ingested between 60–90 min before. Moreover, chronic Arg supplementation should include 1.5–2 g/day for 4–7 weeks in order to improve aerobic performance, and 10–12 g/day for 8 weeks to enhance anaerobic performance.

Proton pump inhibitors (PPI) are suppressors of gastric acid secretion (SGAS) that decrease gastric nitric oxide (NO) formation from nitrite and increase the cardiovascular risk. However, H2 receptor antagonists (H2RA) are considered safer than PPIs. We challenged this notion and hypothesized that both omeprazole (PPI) and ranitidine (H2RA) attenuate the responses to oral nitrite because both drugs increase gastric pH and therefore could decrease nitrite-derived NO formation in the stomach. We examined the blood pressure responses to oral nitrite in hypertensive rats treated with omeprazole, ranitidine, or vehicle. Chemiluminensce-based assays were used to measure gastric NO formation, plasma and gastric concentrations of nitrite, nitrate, and nitrosylated species (RXNO) to clarify the mechanism involved in the effects of SGAS on the responses to oral nitrite. Both drugs increased gastric pH, impaired oral nitrite-induced hypotensive responses, gastric NO formation, and blunted the increases in circulating RXNO concentrations, but not in circulating nitrite and nitrate concentrations. These findings were reproduced in a second study using sodium acetate buffers at pH 3.5, 4.5, and 5.5 to mimic gastric pH found with vehicle, ranitidine, and omeprazole, respectively. Increasing gastric pH impaired oral nitrite-induced hypotensive responses, gastric NO formation, and blunted the increases in circulating RXNO concentrations, but not in circulating nitrite and nitrate concentrations. Our results clearly indicate that SGAS impair nitrite-induced gastric formation of NO and vasoactive RXNO in a pH-dependent manner, thus resulting in impaired responses to oral nitrite. These findings may have several clinical implications, particularly to patients with cardiovascular diseases.

Propofol anesthesia is usually accompanied by hypotension. Studies have shown that the hypotensive effects of propofol increase in patients treated with angiotensin-converting enzyme inhibitors (ACEi). Given that both propofol and ACEi affect nitric oxide (NO) signaling, the present study tested the hypothesis that ACEi treatment induces pronounced hypotensive responses to propofol by increasing NO bioavailability. In this study we evaluated 65 patients, divided into three groups: hypertensive patients chronically treated with ACEi (HT-ACEi; n = 21), hypertensive patients treated with other antihypertensive drugs instead of ACEi, such as angiotensin II receptor blockers, β-blockers or diuretics (HT; n = 21) and healthy normotensive subjects (NT; n = 23). Venous blood samples were collected at baseline and after 10min of anesthesia with propofol 2mg/kg administrated intravenously by bolus injection. Hemodynamic parameters were recorded at each blood sample collection. Nitrite levels were determined by using an ozone-based chemiluminescence assay, while NOx (nitrites+nitrates) levels were measured by using the Griess reaction. Additionally, experimental approaches were used to validate our clinical findings. Higher decreases in blood pressure after propofol anesthesia were observed in HT-ACEi group as compared with those found in NT and HT groups. Consistently, rats treated with the ACEi enalapril showed more intense hypotensive responses to propofol. The hypotensive effects of propofol were associated with increased NO production in both clinical and experimental approaches. Enhanced increases in nitrite levels after propofol anesthesia were observed in HT-ACEi patients compared with NT and HT groups. Accordingly, rats treated with enalapril showed increased vascular NO formation after propofol anesthesia compared with rats receiving vehicle. Our data show that ACEi enhance the hypotensive responses to propofol anesthesia and increase nitrite concentrations. These findings suggest that increased NO bioavailability may account for the enhanced hypotensive effects of propofol in ACEi-treated patients.

RESUMO Objetivo: Avaliar a associação entre os valores da fração exalada de óxido nítrico (FeNO) e do volume expiratório forçado no primeiro segundo (VEF1) e o grau de controle da asma, segundo proposta do Global Initiative for Asthma (GINA), em crianças e adolescentes asmáticos atendidos no Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira da Fundação Oswaldo Cruz(IFF/FIOCRUZ). Métodos: Estudo transversal, com revisão de prontuários de 90 asmáticos entre 7 e17 anos de idade, acompanhados no Ambulatório de Asma do IFF/FIOCRUZ e encaminhados ao setor de Prova de Função Respiratória (PFR) entre março de 2013 e setembro de 2014. Após classificação segundo o GINA, os pacientes realizaram espirometria completa e medida da FeNO. Posteriormente, foram separados em dois grupos: em uso regular e não regular de corticosteroide inalatório (CI), independentemente do padrão ventilatório na espirometria. Resultados: Observou-se associação entre os valores de VEF1 e o grau de controle da asma segundo o GINA (p=0,001) em todos os pacientes analisados, independentemente do uso de CI, mas não houve associação entre os valores de VEF1 e os níveis da FeNO. Conclusões: A correlação observada entre o GINA e o VEF1 reforça a importância da espirometria no seguimento clínico desses pacientes. Embora não tenha sido detectada associação entre o valor da FeNO e o grau de controle da asma e o VEF1,a FeNO pode constituir um método precoce para detectar inflamação nas vias aéreas, antes mesmo dos sintomas e das alterações espirométricas.