Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats / Tratamento com Resveratrol Normaliza a Função Endotelial e a Pressão Arterial em Ratas Ovariectomizadas

Abstract Background: Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). Objective: To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. Methods: 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Results: Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Conclusion: Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats.

Resumo Fundamentos: Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Objetivo: Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a pressão arterial e a função endotelial em ratas adultas jovens ovariectomizadas. Métodos: Foram utilizadas ratas Wistar com 3 meses de idade, distribuídas em 6 grupos: grupos intactas com 60 ou 90 dias, grupos ovariectomizadas com 60 ou 90 dias, grupos ovariectomizadas e tratadas com resveratrol na dose de 10mg/kg de massa corporal por dia, durante 60 ou 90 dias, sendo o número de dias em cada grupo relativo à duração do período experimental. Foi realizado um estudo de reatividade vascular em anéis da aorta abdominal, mensurada a pressão arterial sistólica e quantificada a concentração sérica de óxido nítrico (NO). Resultados: A ovariectomia induziu aumento da pressão arterial 60 e 90 dias após a cirurgia, enquanto a função endotelial decaiu apenas após 90 dias, e não houve diferença na concentração de NO entre os grupos. Apenas o tratamento prolongado com resveratrol (90 dias) foi capaz de melhorar a função endotelial e normalizar a pressão arterial. Conclusão: Nossos resultados sugerem que o tratamento por 90 dias com resveratrol é capaz de melhorar a função endotelial e diminuir a pressão sanguínea em ratas ovariectomizadas.

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Estresse Isolado ou Associado ao Etanol Libera Prostanóides em Aorta de Ratos via ?2-Adrenoceptores / Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via ?2-Adrenoceptor

Fundamento: Estresse e etanol são ambos, independentemente, importantes fatores de risco cardiovascular. Objetivo: avaliar o risco cardiovascular do consumo de etanol e exposição ao estresse, isolados e em associação, em ratos machos adultos. Métodos: Os ratos foram separados em quatro grupos: controle, etanol (20% na água de beber durante seis semanas), estresse (imobilização 1h dia/5 dias por semana/ 6 semanas) e estresse/etanol. As curvas de concentração-resposta à noradrenalina - na ausência e na presença de ioimbina, L-NAME ou indometacina - ou fenilefrina foram determinadas em aortas torácicas com e sem endotélio. EC50 e resposta máxima (n = 8-12) foram comparadas através de ANOVA de dois fatores (two-way) / método de Bonferroni. Resultados: Estresse ou estresse em associação com o consumo de etanol aumentaram as respostas máximas de noradrenalina em aortas intactas. Essa hiper-reatividade foi eliminada pela remoção do endotélio, ou pela presença da indometacina ou ioimbina, mas não foi alterada pela presença de L-NAME. Enquanto isso, o consumo de etanol não alterou a reatividade à noradrenalina. As respostas da fenilefrina em aortas com e sem endotélio também permaneceram inalteradas independentemente do protocolo. Conclusão: O estresse crônico aumentou as respostas aórticas dos ratos à noradrenalina. Esse efeito é dependente do endotélio vascular e envolve a liberação de prostanóides vasoconstritores através da estimulação de α-2 adrenoceptores endoteliais. Além disso, o consumo crônico de etanol pareceu não influenciar as respostas de noradrenalina em aorta de rato, nem modificar o aumento de tais respostas observadas em consequência da exposição ao estresse. .

Background: Stress and ethanol are both, independently, important cardiovascular risk factors. Objective: To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Methods: Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Results: Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Conclusion: Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure. .

Prevalência de dislipidemia em adultos de meia-idade com polimorfismo do gene NOS3 e baixa aptidão cardiorrespiratória / Prevalence of dyslipidemia in middle-aged adults with NOS3 gene polymorphism and low cardiorespiratory fitness

OBJETIVO: Analisar a influência da associação dos polimorfismos do gene da sintase do óxido nítrico endotelial (NOS3) para as posições -786T>C, Glu298Asp e íntron 4b/a e a aptidão cardiorrespiratória sobre as concentrações de nitrito/nitrato, pressão arterial, perfil lipídico e prevalência de doenças cardiometabólicas em adultos. SUJEITOS E MÉTODOS: Noventa e duas pessoas foram divididas de acordo com o genótipo: não polimórficas (NP) e polimórficas (P). Posteriormente, foram subdivididas pela aptidão cardiorrespiratória associada ao genótipo: alta (ANP e AP) ou baixa (BNP e BP). RESULTADOS: Os indivíduos que apresentavam polimorfismo para as posições Glu298Asp+Íntron 4b/a e Glu298Asp+-786T>C e baixa aptidão cardiorrespiratória apresentaram maiores valores de colesterol total e maior prevalência de dislipidemia. CONCLUSÃO: Nossos dados demonstram que os polimorfismos do gene da NOS3 para essas duas associações influenciam os níveis de colesterol plasmático, e essa associação foi mais claramente observada quando os indivíduos apresentavam menor nível de aptidão cardiorrespiratória.

OBJECTIVE: To evaluate the influence of the interaction between endothelial nitric oxide synthase gene (NOS3) polymorphisms at positions -786T>C, Glu298Asp and intron 4b/a, and cardiorespiratory fitness on plasma nitrite/nitrate levels, blood pressure, lipid profile, and prevalence of cardiometabolic disorders. SUBJECTS AND METHODS: Ninety-two volunteers were genotyped for NOS3 polymorphisms at positions (-786T>C and Glu298Asp) and (intron 4b/a) and divided according to the genotype: non-polymorphic (NP) and polymorphic (P). After that, they were subdivided according to the cardiorespiratory fitness associated with genotype: high (HNP and HP) and low (LNP and LP). RESULTS: The subjects with polymorphism for the interactions at positions Glu298Asp + intron 4b/a, and Glu298Asp+-786T>C showed the highest values in total cholesterol, as well as dyslipidemia. CONCLUSION: Our findings show that NOS3 gene polymorphisms at positions -786T>C, Glu298Asp, and intron 4b/a exert negative effects on the lipid profile compared with those who do not carry polymorphisms.

Evaluation of serum nitrate levels in infants and children with congenital heart diseases

This study was carried out on 100 patients having congenital heart disease [CHO], 63 males and 37 females, their age ranged from 4 months to 12.5 years. In addition, 20 apparently healthy children were taken as a control group. This study was done at AI-Azhar University Hospital on patients attending the cardiology and pediatric cardiology outpatient clinic as well as children admitted to the inpatient department. The CHO patients were divided into groups according to: pulmonary artery systolic pressure [PASP] [normal PASP, mild, moderate or severe pulmonary hypertension], presence or absence of heart failure [HF]: [patients with or without heart failure], correction of the cardiac defect: [patients with or without surgical correction] and cyanosis [cyanotic or non-cyanotic CHO]. All patients were subjected to the following: full history taking, complete physical examination [general and cardiac], plain x-ray chest and heart, electrocardiography, echo cardiography and measurement of serum nitrate levels. Our results showed statistically significant differences in serum nitrate levels particulary between patients with severe pulmonary hypertension and those without and between patients with heart failure and those without. The levels were higher in the HF group compared to non-HF group and the control group. No statistically significant differences in serum nitrate levels were found between patients who previously underwent operations for correction of the cardiac defects and those who did not nor between cyanotic and non-cyanotic groups

[Evaluation of serum nitrite, nitrate and malondialdehyde concentrations in preeclampsia]

Preeclampsia is a complication of pregnancy that is associated with high blood pressure with an unknown etiology. There is much evidence that altered endothelial cell functions may play an important role in the pathogenesis of preeclampsia. The aims of this study were to determine serum levels of nitrite, nitrate and malondialdehyde [MDA] in pregnant women with and without preeclampsia. This observational-analytical study was performed in the third trimester of pregnancy on 35 pregnant primiparas with preeclampsia and 35 women with normal blood pressure. The women were recruited for the study among the mothers attending Andimeshk Urban Health Centers during March 2008 to March 2009. Aside from the demographic data, the gestational age and blood pressure were recorded too at the time of blood sampling. Serum levels of nitrite and nitrate were measured by Griess and MDA by thiobarbituric acid reactions. The data were statistically analyzed and compared between the two groups. Serum levels of nitrite, nitrate and MDA, respectively were 12.6 +/- 3.8, 23.8 +/- 8.6 and 9.7 +/- 2.8 micro mol/l in women with preeclampsia and 8.7 +/- 2.5 [p<0.001], 16.4 +/- 5.4 [p<0.01] and 6.34 +/- 1.6 micro mol/l [p<0.001] in the controls. The results depicted significantly higher serum concentrations of the three analyses in pregnant women with preeclampsia relative to the controls. Significantly higher serum concentrations of nitrite, nitrate and MDA in pregnant women with preeclampsia are suggestive of the role of these substances in the pathogenesis of the disease. Use of the three parameters may be useful in the early screening of preeclampsia

Effects of medication with ivermectin, chloroquine and artemether on plasma nitrate / nitrite levels in calves naturally infected with onchocerca gutturosa

In a comparative study involving the use of Ivermectin, Chloroquine and Artemether against Onchocerca gutturosa in calves, the plasma nitrate /nitrite concentration was measured. Following treatment and clearance of skin mf of O. gutturosa, the plasma nitrate/ nitrite concentrations, nor the stable end product of Nitric Oxide [NO] breakdown, rise significantly although it showed short peaks following reduction in dermal mf counts but no clear correlation was detected

Contribuição da apnéia obstrutiva do sono para o estresse oxidativo da obesidade / Obstructive sleep apnea contribution to oxidative stress in obesity

OBJETIVO: O objetivo do trabalho foi verificar a influência da apnéia obstrutiva do sono (AOS) sobre o estresse oxidativo da obesidade e o efeito do pressão positiva de vias aéreas (CPAP) nestes pacientes. MÉTODOS: Os pacientes com IMC > 30 kg/m² foram divididos em: a) grupo 1: dez indivíduos sem AOS; b) grupo 2: dez portadores de AOS que não fizeram o uso do CPAP; e c) grupo 3: nove portadores de AOS que fizeram uso do CPAP durante dois meses. RESULTADOS: O grupo 3 apresentou, após o uso do CPAP, redução na produção de superóxido (SO) [13,2 (10,3-19,6) versus 10,5 (5,8-11,8) nmoles O2-/2×10(6) PMN] e aumento na síntese de nitritos e nitratos séricos [24,5 (16,7-33,5) versus 49,5 (39,3-58,1) µM]. Também foi verificada correlação positiva entre o índice apnéia-hipopnéia (IAH) e a produção de SO (r = 0,726) e negativa entre o IAH e os níveis de nitritos e nitratos séricos (r = -0,867). CONCLUSÕES: O estresse oxidativo presente na obesidade é exacerbado pela AOS e o uso do CPAP promove aumento nos níveis de nitritos e nitratos séricos, bem como reduções na produção de SO neste pacientes.

OBJECTIVE: The aim of this paper was to check the influence of obstructive sleep apnea (OSA) on obesity oxidative stress and CPAP (Continuous Positive Airway Pressure) effect on oxidative stress and in these patients. METHODS: Twenty nine male patients considered obese (BMI > 30kg/m²) were divided into 3 groups: a) Group I: 10 OSA free patients (apnea-hipopnea index (AHI) < 5); b) Group 2: 10 with moderate to serious OSA (AHI > 20); c) Group 3: 9 with OSA from moderate to serious (AHI > 20) using CPAP,, minimum 4 hours/night for 2 months. RESULTS: Significant differences before and after CPAP usage were observed in group 3 in the following variables: reduction of superoxide (SO) production [13,2 (10,3-19,6) vs. 10,5 (5,8-11,8) nmoles O2- /2x10(6) PMN] and increase in serum nitrite/nitrates levels [24,5 (16,7-33,5) vs. 49,5 (39,3-58,1) µM]. Positive correlation between Apnea-Hypopnea Index (AHI) and SO (r = 0,726) and negative correlation was observed between AHI and serum nitrite/nitrates levels (r = - 0,867). CONCLUSIONS: In conclusion, oxidative stress present in obesity is elevated by OSA and CPAP treatment can rise the levels of SO and can decrease serum nitrite/nitrates present in obese patients with OSA.

Methylene blue improves hemodynamic shock but increases lipoperoxidation in severe acute pancreatitis pig model / Azul de metileno melhora as condições hemodinâmicas do choque circulatório, mas aumenta a peroxidação lipídica em um modelo suino de pancreatite aguda grave

PURPOSE: Study hemodynamic pattern and lipoperoxidation during methylene blue (MB) treatment on taurocholate - enterokinase induced acute pancreatitis (AP). METHODS: Thirty pigs were equally divided in control group; MB group; AP group; MB previous AP group; and MB after 90 min of induced AP group. MB was given iv in a bolus dose (2mg.kg-1) followed by maintenance dose (2 mg.kg-1.h-1). Hemodynamic parameters were recorded continuously during 180 min by Swan-Ganz catheter. Blood samples were taken every 60 min to determine arterial and venous nitrate, malondialdehyde (MDA) and amylase. Pancreatic tissue was removed for histopathologic study. RESULTS: In AP group MBP and CO decreased over time 33 percent (p<0.05) and 52 percent (p<0.05), respectively. In MB previous induced-AP group, there was 70 minutes delay (p<0.05) to decrease MBP and CO. In MB group arterial and venous nitrite decreased (p<0.05) over time. MB infusion increased (p>0.05) serum MDA when associated to AP. After induced AP, MB did not reverse MBP and CO decrease. There was no difference in serum amylase and necro-hemorrhagic findings with MB treatment. CONCLUSIONS: In this taurocholate-induced AP model MB treatment delayed hemodynamic shock and decreases serum nitrate levels but increases serum MDA levels. No volemic replacement was done and it may have been a mitigated factor to a poor tissue perfusion and impairment microcirculation. Further investigations are needed to elucidate MB treatment role during AP treatment.

OBJETIVO: estudar o perfil hemodinâmico e a lipoperoxidação durante o tratamento com azul de metileno (AM) de pancreatite aguda (PA) induzida por taurocolato-enteroquinase. MÉTODOS: Trinta porcos foram igualmente divididos em: grupo controle, grupo AM; grupo PA; grupo AM prévio à PA; grupo AM após 90 minutos após a indução da PA. O AM foi administrado sob a forma de bolus EV (2mg.kg-1) seguido por dose de manutenção (2 mg.kg-1.h-1). Os parâmetros hemodinâmicos foram registrados continuamente durante 180 min com auxílio de cateter de Swan-Ganz. Amostras sanguíneas foram colhidas a cada 60 min para a determinação arterial e venosa de nitrato, malondialdeido (MDA) and amilase. Removeu-se tecido pancreático para estudo histopatológico. RESULTADOS: No grupo PA a pressão arterial media (PAM) e o débito cardíaco (DC) diminuíram respectivamente 33 por cento (p<0.05) e 52 por cento (p<0.05) no decorrer do tempo. No grupo AM prévio à indução da PA ocorreu 70 minutes de demora (p<0.05) para as diminuições da PAM e DC. No grupo AM houve diminuição temporal do nitrato arterial e venoso (p<0.05). A infusão de AM aumentou os valores de MDA sérico quando associado a PA (p>0.05). Após a indução da PA a infusão de AM não reverteu as quedas da PA e DC. Não houve diferenças nos níveis de amilase sérica e achados histológicos com o tratamento com o azul de metileno. CONCLUSÕES: No presente modelo de PA induzida por taurocolato o AM retardou o desenvolvimento do choque circulatório, diminuiu os níveis de nitrato mas aumentou os níveis de MDA. Não se realizou nenhum tipo de reposição volêmica que poderia melhorar a perfusão tecidual e melhora da microcirculação. Investigações adicionais são necessárias para elucidar o papel terapêutico do AM no tratamento da PA aguda.

Protective role of sodium selenite on cisplatin induced oxidative and renal stress

Cisplatin is one of the most commonly used antineoplastic agents. Free oxygen radicals are known to play a major role in cisplatin induced renal and oxidative stress. Sodium selenite as an exogenous source of selenium is used for endogenous selenoprotein synthesis to scavenge the free radicals. The study was designed to investigate the possible protective role of sodium selenite in cisplatin induced renal stress, by using biochemical approaches. Adult male Albino Wistar rats were randomly divided into four groups. The control group received distilled water; sodium selenite group received only sodium selenite [1 mg / kg]; cisplatin group received only cisplatin [3 mg / kg]; cisplatin+ sodium selenite group received sodium selenite [1 mg / kg] for 5 alternate days before cisplatin [3 mg / kg] administration. The effects of sodium selenite on cisplatin-induced oxidative and renal stress were evaluated by plasma creatinine, urea, malondialdehyde, nitrate; kidney tissue malondialdehyde, superoxide dismutase and catalase activities. Administration of cisplatin induced significant increases in plasma creatinine, urea and nitrate concentrations showing renal stress. Cisplatin also induced oxidative stress, as indicated by increased kidney tissue concentrations of malondialdehyde, and reduced activities of superoxide dismutase and catalase. Furthermore, treatment with cisplatin caused a marked elevation of kidney weight and decreased body weight. Sodium selenite pretreatment markedly reduced elevated plasma creatinine, urea and nitrate levels and counteracted the deleterious effects of cisplatin on oxidative stress markers. These results indicate that the sodium selenite might have a protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat

Prevalence of anaemia in Tour Sheher Zarghoon, Balochistan

Instead of communicable diseases, developing countries are now seeing serious increase in non-communicable disease and Anemia is one of major problems in developing countries like Pakistan especially in under developed areas like e.g Balochistan. Anaemia is prevalent in certain area of this continent. Anaemia is little bit prevalent in the Urban area of the Balochistan but rural and high altitude areas are still desire its due attention. The people affected belong to rural areas with low socio-economic status and are unable to afford the even economical iron therapy diagnosis, treatment. In some cases bone marrow aspirates and immunodiagnostic facilities are needed for diagnostic purpose. Results showed that prevalence of anemia was high in less than fifteen years of age group, females suffered more with anemia as compared to males in the area

Prevalence of anaemia in Feroza district Khuzdar, Balochistan

Instead of communicable diseases, developing countries are now seeing serious increase in non-communicable disease and Anemia is one of major problems in developing countries like Pakistan especially in under developed areas like e.g Balochistan. Anaemia is prevalent in certain area of this continent. Anaemia is little bit prevalent in the Urban area of the Balochistan but rural and high altitude areas are still desire its due attention. The people affected belong to rural areas with low 50cm-economic status and are unable to afford the even economical iron therapy diagnosis, treatment. In some cases bone marrow aspitates and immunodiagnostic facilities are needed for diagnostic purpose. Results showed that prevalence of anemia was high in more than fifteen years of age group, females suffered more with anemia as compared to males in the area

Antagonic effect of the inhibition of inducible nitric oxide on the mortality of mice acutely infected with Escherichia coli and Bacteroides fragilis

Sepsis, the leading cause of death in intensive care units, is associated with overproduction of nitric oxide (NO) due to inducible NO synthase (iNOS), responsible for some of the pathologic changes. Aminoguanidine (AG) is a selective iNOS inhibitor with reported inconsistent actions in sepsis. To investigate the influence of iNOS, we studied models of acute bacterial sepsis using acute challenges with aerobic (Escherichia coli) and anaerobic (Bacteroides fragilis) bacteria in the presence of AG. Six-week-old, 23 g, male and female BALB/c and C57Bl/6j mice, in equal proportions, were inoculated (ip) with bacteria in groups of 4 animals for each dose and each experiment in the absence or presence of AG (50 mg/kg, ip, starting 24 h before challenge and daily until day 6) and serum nitrate was measured by chemiluminescence. Both types of bacteria were lethal to mice, with an LD50 of 6 nephelometric units (U) for E. coli and 8 U for B. fragilis. Nitrate production peaked on the second day after E. coli inoculation with 8 and 6 U (P < 0.05), but was absent after non-lethal lower doses. After challenge with B. fragilis this early peak occurred at all tested doses after 24 h, including non-lethal ones (P < 0.05). AG-treated mice challenged with E. coli presented higher survival (P < 0.05) and increased LD50. AG-treated mice challenged with B. fragilis had lower LD50 and higher mortality. Control AG-treated animals presented no toxic effects. The opposite effect of iNOS blockade by AG in these models could be explained by restriction of oxygen for immune cells or an efficient action of NO in anaerobic localized infections. The antagonic role of NO production observed in our bacterial models could explain the reported discrepancy of NO action in sepsis.

Estudos hemodinâmicos e da função endotelial em porcas saudáveis após injeção em bolus endovenoso de azul de metileno / Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue / Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue

OBJETIVO: Benefícios clínicos obtidos pelo azul de metileno (AM) no tratamento da vasoplegia induzida pela ação do óxido nítrico (NO) têm sido relatados na sepse, na síndrome da resposta inflamatória sistêmica (SIRS) em cirurgia cardíaca e no choque anafilático, mas a sua segurança é muitas vezes questionada, principalmente relacionada aos seus efeitos hemodinâmicos e à possibilidade de causar disfunção endotelial. O objetivo deste estudo foi examinar os efeitos hemodinâmicos e a função endotelial da infusão endovenosa in vivo do AM em porcos. MÉTODOS: O protocolo de estudo incluiu dois grupos experimentais de porcas fêmeas: Grupo I (Controle) - os animais (n = 6) não receberam AM; Grupo II (AM) - os animais receberam 3 mg/kg de AM em forma de bolus endovenoso. Após quinze minutos de registro dos parâmetros hemodinâmicos os animais foram sacrificados por exsangüinação, e os estudos in vitro foram conduzidos usando segmentos de artérias coronária, hepática, mesentérica superior, renal, para determinar o efeito do AM na função endotelial relacionada com a liberação de NO. Mediu-se também o NO plasmático nos dois grupos experimentais. RESULTADOS: Os resultados obtidos no presente estudo foram: 1) a infusão endovenosa de AM (3,0 mg/kg) não causou nenhuma alteração hemodinâmica significativa; 2) os valores absolutos e porcentuais e nitrito/nitrato plasmático (NOx) não apresentaram diferenças nos dois grupos experimentais; 3) o estudo in vitro dos segmentos arteriais (coronária, hepática, renal e mesentérica superior) não apresentou disfunção endotelial nos dois grupos. Os resultados sugerem que a injeção endovenosa de AM é segura. Esse dado concorda com dados clínicos no qual o AM foi utilizado para tratar a síndrome vasoplégica após circulação extracorpórea, síndrome da resposta infamatória sistêmica (SIRS) e anafilaxia. Os resultados não foram inesperados porque os animais não apresentavam vasoplegia, não se esperando que a inibição da guanilatociclase tenha algum efeito...

OBJECTIVE: Clinical benefit of methylene blue (MB) treating NO-induced vasoplegia has been reported in sepsis, systemic inflammatory response syndrome (SIRS) in cardiac surgery and anaphylactic shock, but its safety is sometimes questioned, mainly regarding its hemodynamic effects and the possibility of causing endothelium dysfunction. To examine the nitric oxide plasma levels and cardiovascular effects of the infusion of MB in vivo and its effects on endothelium-dependent and endothelium-independent in vitro vascular relaxation. METHODS: The study protocol included two experimental groups of female pigs: Group I (Control) - the animals (n=6) did not receive MB; Group II (MB) - the animals received 3 mg/kg of MB intravenous bolus infusion. After fifteen minutes of hemodynamic parameter recording the animals were sacrificed by exsanguination, and in vitro studies were conducted using segments of coronary, hepatic, superior mesenteric and renal arteries, to determine the effect of MB on the arterial endothelium function with regard to NO release. Nitric oxide plasma levels (NOx) were measured in each of the experimental groups. RESULTS: The results obtained in the present investigation were: 1) intravenous infusion of MB (3.0 mg/kg) caused no hemodynamic changes; 2) absolute and percent plasma NOx values did not differ between the experimental groups; and 3) in vitro study of vascular relaxation showed no significant difference between groups. These results show that MB intravenous infusion seems to be safe. This finding agrees with data from clinical experiments where MB was used to treat vasoplegic syndrome after cardiopulmonary bypass, systemic inflammatory response syndrome (SIRS) and anaphylaxis. These results were not unexpected because, as in healthy subjects, hemodynamics is only fine tuned and not fully under NO control; therefore, MB inhibiting guanylyl cyclase is not expected to do anything...

Evidence for the participation of nitric oxide in pemphigus

Pemphigus is an inflammatory autoimmune disorder of the skin. Nitric oxide (NO) is an inflammatory mediator linked to a variety of physiological and pathophysiological phenomena that include skin tumors, psoriasis, urticaria, and atopic dermatitis. Inflammatory cells present in pemphigus lesions are important sources of NO production. We investigated whether NO is involved in pemphigus. A prospective cohort study was conducted at the Dermatology Service of the Hospital Universitário Walter Cantídio of the Federal University of Ceará. All patients seen at the outpatient clinic between August 2000 and July 2001, with a clinically and histologically confirmed diagnosis of pemphigus were included. The median age was 42.5 years (range: 12-69 years) with a male to female ratio of 3:2. Total serum nitrite levels, used as a marker for NO production, were determined by the Griess reaction. Skin biopsies from pemphigus and breast surgery (control) patients were used for the detection of the inducible NO synthase (iNOS) by immunohistochemistry. Twenty-two (22) patients with pemphigus and eight (8) controls who did not differ in demographic characteristics were included. Total serum nitrite levels were significantly higher (>7 æmol/L) in pemphigus patients compared to controls (<6 æmol/L), regardless of the severity of the clinical activity of pemphigus (P < 0.0001). All pemphigus biopsies presented increased immunostaining for iNOS that was not detected in normal skin samples. These data are the first to demonstrate that pemphigus patients display increased serum NO levels that are associated with increased iNOS expression in the affected skin.

Neurohormonal changes in medical students during academic srtess

Academic stress is a good model of psychological stress in humans and is thus useful for studying psychoneurohormonal changes. The aim of the current study was to examine the effect of academic examination stress on activation of the hypothalamus-autonomic nervous system [HANS] and the hypothalamic-pituitary-adrenocortical [HPA] axis, through the measurements of changes in neuro-hormones during final exams as compared to the pre-exam baseline. Forty-eight first- and second-year female medical students participated. Plasma leptin, neuropeptide Y [NPY], nitrite, nitrate, andrenomedullin, cortisol and adrenocorticotropic hormone [ACTH] were measured at baseline and during final examinations. Plasma levels of cortisol, ACTH, NPY, adrenomedullin, nitrite and nitrate increased during times of academic stress as compared to baseline levels. However, only plasma leptin level was decreased during the academic stress as compared to baseline, probably through a negative feedback mechanism resulting from sympathetic stimulation. The results indicate that both the HANS and HPA are involved in this type of stress and both are activated at the same time. Academic stress induced significant neurohormonal changes. Leptin, NPY, nitrite, nitrate, adrenomedullin, cortisol and ACTH can be considered part of a complex mosaic model of the neuroendocrine system during academic stress

Serum nitrate levels as an index of endothelial function in pre-eclamsia and normal pregnancy.

The study was conducted in St. John's Medical College Hospital and Department of Physiology, with the aim of studying the serum nitrate levels in pre-eclampsia and normal pregnancy. The total number of subjects studied in various groups were 159, control (n = 55), first trimester (n = 13), second trimester normal (n = 42), second trimester pre-eclampsia/PET (n = 5), third trimester normal (n = 32), third trimester pre-eclampsia/PET (n = 12). The serum nitrate was measured by one step enzymatic assay using Nitrate reductase from Aspergillus species. The nitrate levels in the third trimester pre-eclamptic group was found to be significant lower (P = 0.02), as compared to normal subjects, however the renal functions were normal in all the subjects.

Assessment of nitric oxide and prostaglandins levels in different pathological types of glomerular disease

The objective of this study was to evaluate plasma nitrite and nitrate as well as urinary nitrite levels in forty cases with different glomerular disorders. In addition, serum thromboxane A2 [TXA2] and prostacyclin 12 [PGI2] levels were evaluated in these cases in comparison to 20 healthy control subjects. The effect of steroid therapy on the above mentioned parameters was also evaluated. The results revealed that urinary nitrite level was significantly elevated among patients compared to control. The elevation was observed in diabetic nephropathy as well as proliferative forms of glomerular disease such as lupus nephritis and mesangioproliferative GN. However, plasma nitrite, nitrate and serum cGMP levels were similar in patients compared to the control levels. TXA2 level exhibited significant elevation in patients, whereas serum PGI2 showed significant decrease in its level among cases as compared to control subjects. Steroid therapy was demonstrated to have no effect on all of the studied parameters. The study concluded that the data indicated that NO might play a role in the pathogenesis of proliferative glomerular disease and diabetic nephropathy. The demonstration of normal level of urinary nitrite in non proliferative GN suggests that enhanced NO production is not the sole cause of proteinuria in these cases. Further studies are, therefore, needed to examine the exact role of NO in pathogenesis of glomerular injury. The significant elevation of TXA2 level together with the significant decrease in serum PGI2 should be thoroughly investigated regarding the renal hemodynamics, the extent of proteinuria and the thromboembolic tendency reported in these cases

Role of nitric oxide in essential hypertension and its relationship to ventricular hypertrophy

Patients with essential hypertension exhibit blunted endothelium dependent vasodilator response, which is largely attributable to reduced bioavailability of nitric oxide [NO]. Therefore, this study was designed to estimate, more directly, nitric oxide production in patients with essential hypertension and to examine the possible association between NO and left ventrivular [LV] and vascular hypertrophy. The level of serum total nitrite and nitrate, the stable end products of NO oxidation, was measured in 40 hypertensive patients [group I] and 15 control subjects [group II]. Hypertensive patients were divided according to LV geometry into 21 patients with left ventricular hypertrophy [LVH] [group Ia] and 19 patients with normal LV geometry [group Ib]. Serum total nitrite and nitrate level was significantly lower in patients with essential hypertension compared to normal controls [25.07 +/- 8.78 micro mol/L verses 39.36 +/- 7.07 micro mol/L] [p<0.001]. It was significantly lower in patients with LVH compared to patients without LVH [20.50 +/- 8.07 micro mol/L versus 30.11 +/- 6.60 micro mol/L] [p<0.001]. There was a significant negative correlation between serum total nitrite and nitrate level and LVMI, IVS and PWT [p<0.001]. This study also showed a significant positive correlation between LVMI and carotid, femoral and aortic media to lumen [M/L] ratio [p<0.001]. Serum total nitrite and nitrate level was significantly lower in patients with higher M/L ratio and there was a significant negative correlation between serum total nitrite and nitrate level and carotid, femoral and aortic M/L ratio [p<0.01, p<0.001 and p<0.05 respectively]. It was concluded that NO level is reduced in patients with essential hypertension and that this reduced level has a role in the pathogenesis of left ventricular and vascular hy[ertrophy in patients with essential hyptertension