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. .

Ativação adrenérgica intramiocárdica na cardiomiopatia chagásica e doença arterial coronariana / Intramyocardial adrenergic activation in chagasic cardiomyopathy and coronary artery disease / Activación adrenérgica intramiocárdica en la cardiomiopatía chagásica y enfermedad arterial coronaria

FUNDAMENTO: A norepinefrina miocárdica está alterada na disfunção ventricular esquerda. Em pacientes com cardiomiopatia chagásica (CC), essa questão ainda não foi discutida. OBJETIVO: Determinar o nível de norepinefrina (NE) miocárdica em pacientes com CC e compará-la em pacientes com doença arterial coronariana (DAC) e relacionar NE miocárdica com a fração de ejeção do ventrículo esquerdo (FEVE). MÉTODOS: Estudamos 39 pacientes com CC, divididos em grupo 1: 21 indivíduos com FEVE normal e grupo 2: 18 com FEVE diminuída. Dezessete pacientes com DAC foram divididos em grupo 3: 12 indivíduos com FEVE normal e grupo 4: 5 indivíduos com FEVE diminuída. Ecocardiografia bidimensional foi usada para medir a FEVE. A NE miocárdica foi determinada através de Cromatografia Líquida de Alta Eficiência (HPLC). RESULTADOS: A NE miocárdica na CC com e sem disfunção ventricular foi 1,3±1,3 e 6,1±4,2 pg/μg de proteína não-colagenosa, respectivamente (p<0,0001); na DAC com e sem disfunção ventricular, foi 3,3±3,0 e 9,8±4,2 pg/μg de proteína não-colagenosa, respectivamente (p<0,0001). Uma correlação positive foi observada entre a FEVE e a concentração de NE miocárdica em pacientes com CC (p<0,01; r = 0,57) e também naqueles com DAC (p<0,01; r=0,69). Uma diferença significante foi demonstrada entre as concentrações de NE em pacientes com FEVE normal (grupos 1 e 3; p = 0,0182), mas nenhuma diferença foi observada em pacientes com FEVE diminuída (grupos 2 e 4; p = 0,1467). CONCLUSÃO: Pacientes com CC e fração de ejeção global normal apresentam uma denervação cardíaca precoce, quando comparados à pacientes com doença arterial coronariana.

BACKGROUND: Myocardial norepinephrine is altered in left ventricular impairment. In patients with Chagas' cardiomyopathy (CC), this issue has not been addressed. OBJECTIVE: To determine the level of myocardial norepinephrine in patients with CC and compare it in patients with coronary artery disease, and to relate myocardial norepinephrine to left ventricular ejection fraction (LVEF). METHODS: We studied 39 patients with CC, divided into group 1: 21 individuals with normal LVEF and group 2: 18 individuals with decreased LVEF. Seventeen patients with coronary artery disease were divided into group 3: 12 individuals with normal LVEF and group 4: 5 individuals with decreased LVEF. Two-dimensional echocardiography was used to measure LVEF. Myocardial norepinephrine was determined by high-performance liquid chromatography. RESULTS: Myocardial norepinephrine in CC with and without ventricular dysfunction was 1.3±1.3 and 6.1±4.2 pg/μg noncollagen protein, respectively (p<0.0001); in coronary artery disease with and without ventricular dysfunction, it was 3.3±3.0 and 9.8±4.2 pgμg noncollagen protein, respectively (p<0.0001). A positive correlation was found between LVEF and myocardial norepinephrine concentration in the patients with Chagas' cardiomyopathy (p<0.01, r = 0.57) and also in those with coronary artery disease (p<0.01, r=0.69). A significant difference was demonstrated between norepinephrine concentrations in patients with normal LVEF (groups 1 and 3; p = 0.0182), but no difference was found in patients with decreased LVEF (groups 2 and 4; p = 0.1467). CONCLUSION: In patients with Chagas' cardiomyopathy and normal global ejection fraction there is an early cardiac denervation, when compared to coronary artery disease patients.

FUNDAMENTO: La norepinefrina miocárdica está alterada en la disfunción ventricular izquierda. En pacientes con cardiomiopatía chagásica (CC), esa cuestión aun no fue discutida. OBJETIVO: Determinar el nivel de norepinefrina (NE) miocárdica en pacientes con CC y compararla en pacientes con enfermedad arterial coronaria (EAC) y relacionar NE miocárdica con la fracción de eyección del ventrículo izquierdo (FEVI). MÉTODOS: 39 pacientes con CC, divididos en grupo 1: 21 individuos con FEVI normal y grupo 2: 18 con FEVI disminuida. Diecisiete pacientes con EAC fueron divididos en grupo 3: 12 individuos con FEVI normal y grupo 4: 5 individuos con FEVI disminuida. Ecocardiografía bidimensional fue usada para medir la FEVI. La NE miocárdica fue determinada a través de Cromatografía Líquida de Alta Eficiencia (HPLC). RESULTADOS: La NE miocárdica en la CC con y sin disfunción ventricular fue 1,3±1,3 y 6,1±4,2 pg/µg de proteína no colagenosa, respectivamente (p<0,0001); en la EAC con y sin disfunción ventricular, fue 3,3±3,0 y 9,8±4,2 pg/µg de proteína no colagenosa, respectivamente (p<0,0001). Una correlación positiva fue observada entre la FEVI y la concentración de NE miocárdica en pacientes con CC (p<0,01; r=0,57) y también en aquellos con EAC (p<0,01; r=0,69). Una diferencia significativa fue demostrada entre las concentraciones de NE en pacientes con FEVI normal (grupos 1 y 3; p = 0,0182), pero ninguna diferencia fue observada en pacientes con FEVI disminuida (grupos 2 y 4; p = 0,1467). CONCLUSIONES: Pacientes con CC y fracción de eyección global normal presentan una denervación cardíaca precoz, cuando son comparados a pacientes con enfermedad arterial coronaria.

Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera.

BACKGROUND & OBJECTIVES: The monoaminergic systems which exert a modulatory role in memory processing, are disturbed in Alzheimer's disease (AD) and Moringa oleifera (MO) has been shown to exert its effect in CNS by altering the brain monoamines. The present study aims to see whether chronic oral treatment of ethanolic extract of MO leaves can alter the brain monoamines (norepinephrine, dopamine and serotonin) in distinct areas of brain in rat model of AD caused by intracerebroverticle (ICV) infusion of colchicine and hence can provide protection against monoaminergic deficits associated with AD. METHODS: Rats were given ICV infusion of colchicine (15 microg/5microl) and MO leaf alcoholic extract was given in various doses. The effective dose was standardized by radial arm maze (RAM) training. From the selected dose of 250 mg/kg body weight, the biochemical estimations and EEG studies were performed. RESULTS: Stereotaxic ICV infusion of colchicine significantly impaired the RAM performance together with decrease in norepinephrine (NE) level in cerebral cortex (CC), hippocampus (HC) and caudate nucleus (CN). Dopamine (DA) and serotonin (5-HT) levels were decreased in CC, HC and CN. The EEG studies showed a decrease in beta and alpha waves and increase in biphasic spike wave pattern in experimental Alzheimer rat model. Treatment with MO extract markedly increased the number of correct choices in a RAM task with variable alteration of brain monoamines. The EEG studies showed an increase in beta waves and a decrease in spike wave discharges. INTERPRETATION & CONCLUSION: Our results showed that brain monoamines were altered discreetly in different brain areas after colchicine infusion in brain. After treatment with MO, leaf extract the monoamine levels of brain regions were restored to near control levels. Our findings indicated that MO might have a role in providing protection against AD in rat model by altering brain menoamine levels and electrical activity.

Comparative neurochemical changes associated with chronic administration of typical and atypical neuroleptics: implications in tardive dyskinesia.

An important goal of current neuroleptic research is to develop antipsychotic compounds with the low incidence of extrapyramidal side effects. The therapeutic success and less side-effect of atypical anti-psychotics such as clozapine and risperidone has focused the attention on the role of receptor systems other than dopaminergic system in the pathophysiology of neuroleptics-associated extrapyramidal side effects. The present study compares the effect of chronic administration of typical and atypical antipsychotics on neurochemical profile in rat forebrain. The study was planned to study changes in extracellular levels of norepinephrine, dopamine and serotonin in forebrain region of brain and tried to correlate them with hyperkinetic motor activities (vacuous chewing movements (VCM's), tongue protrusions and facial jerking) in rats, hall mark of chronic extrapyramidal side-effect of neuroleptic therapy tardive dyskinesia. Chronic administration of haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) resulted in significant increase in orofacial hyperkinetic movements where as clozapine and risperidone showed less significant increase in orofacial hyperkinetic movements as compared to control. There were also significant decrease in the extracellular levels of neurotransmitters dopamine, norepinephrine and serotonin in fore-brain as measured by HPLC/ED after chronic administration of haloperidol and chlorpromazine. Chronic administration of atypical neuroleptics clozapine and risperidone resulted in the decrease in extracellular concentration of dopamine and norepinephrine but the effect was less significant as compared to typical drugs. However, treatment with atypical neuroleptics resulted in 3 fold increase in serotonin levels as compared to forebrain of control rats. Typical and atypical neuroleptics showed varying effects on neurotransmitters, especially serotonin which may account for the difference in their profile of side effects (Tardive dyskinesia).

Stress responses after major surgery in infant: comparison of two analgesic regimens of morphine

Infants under 1 year classified to receive either continuous morphine [CM, 10 microg/kg/h] with three-hourly placebo boluses or intermittent morphine [IM, 30 microg/kg every 3h] with a placebo infusion for postoperative analgesia. Plasma concentration of norepinephrine, insulin, glucose and lactate were measured before and at the end of surgery, 12h and 24h after surgery. Pain was assessed with the comfort scale and visual analogue scale [VAS] with the availability or additional morphine doses. Minor differences occurred between the three groups, IM group in infants aged 6m-1 yr [group 3] having a higher blood glucose concentration [p = 0.003] mean arterial pressure [p = 0.02] and comfort score [p = 0.02] than the CM group. In the neonates, preoperative plasma. Concentration of norepinephrine [p = 0.01] and lactate [p < 0.001] were significantly higher, while the postoperative plasma concentration of insulin significantly higher [p < 0.005] than in the group II and III. Postoperative pain scores [p < 0.003] and morphine consumption [p < 0.001] were significantly lower in the neonates [Group I] than in the group II and III. The study shows that continuous infusion of morphine does not provide any major advantages over intermittent morphine boluses for postoperative analgesia in neonates and infants

An improved histochemical technique for differentiating adrenaline-and noradrenaline-containing cells

Background. Sevki's histochemical technique allows specific staining of catechomamine-containing cells, yet discrimiantion between adrenaline-(ADR-) cells and noradrenaline-(NOR-) cells is unrealiable, being based on hue differences. Methods. In this work, histochemical differentiation of ADR- and NOR-cells in rat adrenal medulla was carried out by introducing two modifications to Sevki's technique: 1) employment of aged Giemsa solution, and 2) addition of an alkaline differentiating step. Results. With these changes, ADR-cell stained brown, whereas NOR-cells were deep-green, resulting in a clear-cut differentiation. Conclusions. The modified technique permits to differentiate ADR- from NOR-cells in the adrenal medulla using only a bright field microscope without any sophisticated equipment. The present procedure is inexpensive and easy to carry out

Alteraçöes da pressäo arterial e da freqüência cardíaca provocadas pela administraçäo intravascular de cloridrato de lidocaína a 2 por cento associado ao cloridrato de noradrenalina 1:50.000 (xylocaína), antes e após admistraçäo intravascular de diazepam, em cäes / Blood pressure and heart rate changes by intravascular administration of 2 por cento lidocaine hydrochrloride associated to 1:50.000 norepinephrine hydrochrloride (xylocaine), before and after intravascular administration of diazepam in dogs

O objetivo deste estudo foi avaliar as alteraçöes das pressöes arteriais sistólica, diastólica e média e da freqüência cardíaca, provocadas pela administraçäo intravascular de cloridrato de lidocaína a 2 por cento associado ao cloridrato de noradrenalina 1:50.000 (Xylocaína), nas doses proporcionais a 1 e 3 cartuchos, antes e após administraçäo intravascular de diazepam (Diazepam), em cäes (Canis familares) sob efeito de anestesia geral. Foram avaliados também os tempos em que elas ocorreram em sua máxima intensidade. Para a dose proporcional a 1 cartucho anestésico de 1,8ml, ou seja, 0,51mg/Kg de cloridrato de lidocaína e 0,51µg/Kg de cloridrato de noradrenalina, foram utilizados 10 cäes. Para a dose proporcional a 3 cartuchos anestésicos (5,4ml), ou seja, 1,53mg/Kg de cloridrato de lidocaína e 1,53µg/Kg de cloridrato de noradrenalina, foram utilizados 7 cäes. A dose utilizada para o Diazepam foi proporcional a 5mg, ou seja, 0,071mg/Kg. As mensuraçöes foram obtidas continuadamente por meio de método invasivo e registro eletrocardiográfico (eletrofisiógrafo Beckman - Dynograph). Foram estabelecidos como valores controle aqueles imediatamente anteriores à 1ª e à 2ª administraçäo intravascular da Xylocaína. Os valores registrados foram submetidos à análise estatística utilizando-se testes "T" de Student. As pressöes arteriais sistólica, diastólica e média apresentaram alteraçöes clinicamente importantes e estatisticamente significantes provocadas pela administraçäo intravascular da Xylocaína, antes e após administraçäo intravascular de diazepam, em ambas as doses utilizadas. As alteraçöes máximas das variáveis cardiovasculares estudadas ocorreram, praticamente, durante o primeiro minuto após o ínicio da administraçäo do anestégico local

Epinephrine as a metabolic regulatory hormone in irradiated rats

The role of epinephrine as a regulatory hormone was examined in normal and irradiated rats. Epinephrine was intraperitoneally injected into rats at a concentration of 200 microg/kg body weight. Epinephrine was injected either 15 minutes before or just after whole body gamma irradiation 6 Gy [single dose]. The variations in serum epinephrine, norepinephrine, triglycerides, lipase activity, glucose and lactic acid were selected as biochemical markers in this study. Biochemical estimations were undertaken at 1 hr, 4 hrs, 1, 3 and 7 days after treatment [after irradiation]. The data obtained revealed that the treatment of normal rats with epinephrine induced a significant increase in serum epinephrine level 1 hr after injection, while the level of norepinephrine significantly increased at 4 hrs. Lipase activity significantly increased on the 1[st] hr post treatment. A significant decrease in the level of triglycerides was recorded 1 and 4 hrs post treatment. Serum glucose significantly increased at 1 and 4 hrs post treatment, while no significant changes were recorded for lactic acid. In gamma irradiated rats, the level of serum epinephrine significantly decreased at 1 hr followed by significant increases recorded at 1, 3, and 7 days after irradiation. Norepinephrine levels significantly decreased after irradiation during all the experimental time periods. The levels of triglycerides show significant increases accompanied by a decrease in lipase activity. A temporary decrease of glucose level was recorded at 1 hr followed by significant increase recorded at 1, 3, and 7 days post irradiation. Lactic acid levels show significant increase during all the experimental time periods. The data revealed that treatment of rats, with epinephrine, either pre or post irradiation, has diminished the radiation induced changes in most of the studied parameters. Accordingly, it could be concluded that epinephrine could exert a beneficial protective role against certain radiation induced disorders through acting as a regulatory hormone of the metabolic pathways

Incriase of the serotonin metabolite, 5-hydroxyindoleacetic acid, in cerebro-spinal fluid and spinal cord of bovines affected with the paraplegic syndrome

The paraplegic syndrome of bovines is a condition characterized by impairment of locomotion, hypoalgesia and finally death within 72 h. The pathogenesis of the syndrome has not been established. In the present work we determined the levels of monoamines and their metabolites in cerebro-spinal fluid and spinal cord of affected animals in order to investigate the functional state of these neurotransmitters. The content of the main metabolite of serotonin, 5-hydroxyindoleacetic acid, was elevated in the cerebro-spinal fluid and in the gray matter of the spinal cord of paraplegic bovines. Serotonin content in the spinal cord did not differ with respect to control animals, but was decreased in the cerebro-spinal fluid of affected animals. Modifications in the noradrenergic system were also observed, but were less consistent, for which reason further studies are needed. These observations indicate an increase in the turnover rate of serotonin in the paraplegic syndrome. The meaning of the described alterations is unknown at the moment

Investigaciones de los neurotransmisores 5-hidroxitriptamina, noradrenalina y dopamina, en mucosa gastroduodenal: correlación clínica e histológica / Determination of the neurotransmitters 5-hydroxytryptamine, noradrenaline, and dopamine in gastroduodenal mucosa: clinical and histologic correlation

Se estudiaron las concentraciones (pg/mg de tejido de los neurotransmisores (NT) 5-Hidroxitriptamina (5HT), Noradrenalina (NA) y Dopamina (DA) en mucosa del fundus gástrico (F), antro (A) y bulbo duodenal (D) de 21 paciente con mucosa normal y con diversos grados de inflamación crónica. Se correlacionaron las concentraciones de los NT entre sí, en conjuntos en cada región y con parámetros clínicos, de motilidad indirectos e histológicos. Los valores promedios hallados en cada región fueron para 5HT: F=940+/-457, en A=787+/-407 y en D=601+/-272; para NA en F=217+/-138, en A=228+/-126 y en D=245+/-118; y para DA en F=50+/-32, en A=46+/-31 y en D=53+/-45. Se observó que a mayores infiltrados inflamatorios en bulbo duodenal se encontraron mayores concentraciones de DA (r=0,94). Ningún otro parámetro tuvo relación significativa con las variaciones de los NT. Se pudo establecer que las variaciones de las concentraciones de los NT de la mucosa del antro gástrico están más asociadas a las del bulbo duodenal que a las del fundus gástrico

Brain monoamines during footshock-induced aggression in paired rats.

Regional brain monoamine concentrations were investigated following footshock induced fighting behaviour in paired rats, by a spectrophotofluorometric method. The dopamine (DA) levels of the diencephalon-midbrain (DM), and that of the caudate nucleus (CN), were significantly augmented as compared to unshocked but paired rats, the increase being substantially more in DM. Noradrenaline (NA) concentrations of both DM and pons-medulla (PM) increased to almost similar extents, though the data remained statistically insignificant in comparison to controls. The 5-hydroxytryptamine (5HT) of both DM and PM, however, recorded a decrease, which was statistically significant in the latter brain area. The biochemical data are consonant with the reported facilitatory effect of central DA, and the inhibitory role of central 5HT, in experimental aggression. The observed changes in NA levels, for which a role in experimental aggression remains equivocal, may be due to the stress of footshock kept minimal due to the coping factor of fighting in response to the shock.

HPLC determination of norepinephrine, 5-hydroxytyramine and 5-hydroxytryptamine in rat brain using sodium dodecyl sulphate as ion-pair

1. A simple HPLC method using sodium dodecyl sulfate (SDS) and elelctrochemical detection for the determination of norepinephrine (NE), 5-hydroxytyramine (DA) and 5-hydroxytryptamine (5-HT) in brain regions is described. 2. the tissue extraction procedure involved only two stepes: protein precipitation with perchloriac acid and pH adjustment to near 3.0. When used in combination with methanol as ion-pair in the mobile phase, sodium dodecyl sulgate effectively separated NE (6.6 min), epinephrine (EPI), 7.9 min), DA (14.3 min) and 5-HT (29.5 min) and the high methanol concentration used prevente the overlapping of the metabolites and monoamines in their chromatographic peaks. 3. the method was sensitive (40 to 70 pg of monoamine can be quantified) and reproducible and the values obtained for cortex, hippocampus, striatum and substantia nigra were consoant with most literature data

Efectos del tratamiento electroconvulsivo sobre el contenido en monoamimas en tejido cerebral de ratas tratadas con reserpina / Effects of electroconvulsive therapy on the monoamine contents in the brain tissue of rats under reserpine treatment

En este trabajo se presentan los resultados obtenidos en cuanto a los niveles de noradrenalina (NA), dopamina (DA) y 5-hidroxitriptamina (5HT) en cuatro porciones de cerebro de ratas tratadas con tratamiento electroconvulsivo y con reserpina. Se utilizó este fármaco debido a su efecto inhibitorio en la recaptura de las monoaminas (MA), lo cual conlleva a una depleción de las vesículas monoaminérgicas. Observamos disminución en los niveles de las tres MA en diferentes porciones del cerebro de las ratas que recibieron el tratamiento electroconvulsivo sólo y la reserpina, comparándolas con sus controles

Effects of anterodorsalis thalami nucleus lesion on adrenal function in rats

La lesión bilateral de los núcleos anterodorsales talámicos produjo un aumento significativo en la concentración de corticosterona adrenal y plasmatica, mientras que las catecolaminas adrenales disminuyeron en respuesta a la lesión de los núcleos