RESUMO
Cardiac tissue is densely innervated by sensory neurons that are believed to play important modulatory roles in cardiac functions. In this study, pretreatment of neonate rats with capsaicin was performed. In adult rats, cardiomyocyte size and amount of fibrous tissue in left ventricles as well as in vitro coronary flow were evaluated. The chronotropic and inotropic responses to beta-adrenoceptor agonists (norepinephrine and isoproterenol), muscarinic agonists (carbachol and pilocarpine), and calcitonin gene-related peptide (CGRP) were also investigated with the use of the isolated right atria preparation. Capsaicin pretreatment significantly (P<0.05) reduced both basal coronary flow (18% reduction) and cardiomyocyte size (34% reduction) without affecting the amount of fibrous tissues in the left ventricles. The positive inotropic and chronotropic effects in response to norepinephrine in the isolated rat heart did not significantly differ between control and capsaicin-treated rats. Similarly, the positive chronotropic effects in response to norepinephrine, isoproterenol, and CGRP as well as the negative chronotropic responses to carbachol and pilocarpine in the isolated right atria were not affected by capsaicin pretreatment. Our data are consistent with the suggestion that reductions of both basal coronary flow and cardiomyocyte size seen in hearts from capsaicin-pretreated rats may be consequences of CGRP depletion. The cardiomyocyte size reduction produced by capsaicin treatment may be related to a modulatory role of CGRP as a growth factor.
Assuntos
Circulação Coronária/fisiologia , Miocárdio/citologia , Neurônios Aferentes/fisiologia , Função Ventricular , Agonistas Adrenérgicos beta/farmacologia , Animais , Pressão Sanguínea , Capsaicina/farmacologia , Tamanho Celular , Ventrículos do Coração/inervação , Isoproterenol/farmacologia , Masculino , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Vasoconstritores/farmacologiaRESUMO
The long-term administration of nitric oxide synthesis inhibitors induces arterial hypertension accompanied by left ventricular hypertrophy and myocardial ischemic lesions. Because the enhancement of sympathetic drive has been implicated in these phenomena, the current study was performed to determine the potency of beta-adrenoceptor agonists and muscarinic agonists on the spontaneous rate of isolated right atria from rats given long-term treatment with the nitric oxide inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Atrial lesions induced by long-term treatment with L-NAME were also evaluated. Long-term L-NAME treatment caused a time-dependent, significant (P<0.05) increase in tail-cuff pressure compared with control animals. Our results showed that the potency of isoproterenol, norepinephrine, carbachol, and pilocarpine in isolated right atria from rats given long-term treatment with L-NAME for 7, 15, 30, and 60 days was not affected as compared with control animals. Addition of L-NAME in vitro (100 microl/L) affected neither basal rate nor chronotropic response for isoproterenol and norepinephrine in rat heart. Stereological analysis of the right atria at 15 and 30 days revealed a significant increase on amount of fibrous tissues in L-NAME-treated groups (27+/-2.3% and 28+/-1.3% for 15 and 30 days, respectively; P<0.05) as compared with the control group (22+/-1.1%). Our results indicate that nitric oxide does not to interfere with beta-adrenoceptor-mediated and muscarinic receptor-mediated chronotropic responses.
Assuntos
Pressão Sanguínea/fisiologia , Inibidores Enzimáticos/farmacologia , Átrios do Coração/fisiopatologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Função Ventricular Direita , Animais , Pressão Sanguínea/efeitos dos fármacos , Masculino , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/fisiologia , Ratos , Ratos Wistar , Função Ventricular Direita/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the efficiency of mitomycin C (MMC) in limiting the postoperative inflammatory response and scarring after strabismus surgery. METHODS: A prospective, two-stage, masked, controlled trial was conducted. In the first stage, the inflammatory response at the extraocular muscle reattachment site was increased after inferior rectus recession in eight rabbits. In the second stage, MMC (0.4 mg/ml) was applied during surgery to the eyes of 22 rabbits with inferior rectus recession. As a control, contralateral eyes were treated with saline solution. Seven weeks later, exenteration was performed, and the sites of muscle reattachment were processed for histologic examinations. The sums of the areas of the granulomas in the extraocular muscle reattachment sites of control and treated eyes were compared. RESULTS: There was no significant inhibitory effect of MMC on the inflammatory response of treated eyes compared with that of control eyes. CONCLUSIONS: The intraoperative use of MMC (0.4 mg/ml) was not effective in controlling the postoperative inflammatory response in rabbit eyes after extraocular muscle surgery. These data do not support the hypothesis that MMC reduces postoperative adhesions after strabismus surgery.
Assuntos
Antimetabólitos/uso terapêutico , Granuloma/prevenção & controle , Mitomicina/uso terapêutico , Músculos Oculomotores/patologia , Complicações Pós-Operatórias/prevenção & controle , Estrabismo/cirurgia , Animais , Cicatriz/patologia , Cicatriz/prevenção & controle , Granuloma/patologia , Cuidados Intraoperatórios/métodos , Músculos Oculomotores/cirurgia , Complicações Pós-Operatórias/patologia , CoelhosRESUMO
Nitro-L-arginine methyl ester (0.15 mumol/paw) significantly reduced both bradykinin- and 5-hydroxytryptamine-induced rat paw oedema. At this dose, L-arginine (L-Arg), D-Arg and nitro-D-arginine methyl ester had no effect on the oedematogenic responses induced by these agents. Nitro-L-arginine methyl ester, nitro-D-arginine methyl ester, L-Arg, D-Arg, L-arginine methyl ester and L-arginine ethyl ester, at the dose of 15 mumol/paw, significantly potentiated both bradykinin- and 5-hydroxytryptamine-induced oedema. This potentiation was not observed in animals treated with both mepyramine and methysergide or in animals chronically treated with compound 48/80. Nitro-L-arginine methyl ester (0.3-3 mM) and L-Arg (0.3-3 mM) released small amounts (< 10%) of histamine from rat peritoneal mast cells when compared to compound 48/80-induced degranulation (> 40%). Histamine release was quantified by radioimmunoassay since nitro-L-arginine methyl ester and L-Arg interfere with the fluorometric assay. The potentiation of paw oedema observed with higher doses of all arginine analogues is caused by in vivo mast cell degranulation and is probably due to the cationic charge of these substances.
Assuntos
Arginina/análogos & derivados , Inflamação/imunologia , Mastócitos/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Animais , Arginina/farmacologia , Bradicinina/farmacologia , Edema/induzido quimicamente , Edema/imunologia , Membro Posterior , Liberação de Histamina/efeitos dos fármacos , Masculino , Mastócitos/metabolismo , Metisergida/farmacologia , NG-Nitroarginina Metil Éster , Pirilamina/farmacologia , Radioimunoensaio , Ratos , Ratos Wistar , Serotonina/metabolismo , Serotonina/farmacologiaRESUMO
The effect of neonatal capsaicin (8 methyl-N-vanillyl-6-nonenamide) treatment on the leucocyte infiltration into the airways and pleural cavity was investigated in rats actively sensitized with ovalbumin. The animals were neonatally injected with either capsaicin (50 mg/kg, s.c., 2nd day of life) or vehicle (10% ethanol and 10% Tween 80). At adult ages, the animals were actively sensitized with ovalbumin (200 microg, s.c.) and 14 days later they were intratracheally (or intrapleurally) challenged with ovalbumin. The substance P level in bronchoalveolar lavage fluid of the capsaicin group was reduced by >90% compared to control group (vehicle), confirming the efficacy of capsaicin treatment. In the capsaicin group, the number of neutrophils (but not of eosinophils and mononuclear cells) in bronchoalveolar lavage fluid of sensitized animals was significantly higher than the control group. Intrapleural injection of ovalbumin in sensitized rats caused a significant neutrophil influx at 6 h that was markedly increased in the capsaicin-pretreated animals compared to control group. The counts of eosinophils and mononuclear cells in the pleural exudates did not differ significantly between capsaicin and control groups. The increased levels of immunoglobulin (Ig)E, IgG1 and IgG2a anti-ovalbumin antibodies in serum of sensitized rats did not differ between capsaicin and control groups. In conclusion, the exacerbated pulmonary neutrophil recruitment caused by the capsaicin neonatal treatment is unrelated to increase in serum immunoglobulin antibodies, and suggests a protective role for C-fibers in attenuating the allergic neutrophil infiltration.
Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Capsaicina/farmacologia , Leucócitos/efeitos dos fármacos , Fibras Nervosas/fisiologia , Pleura/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Anticorpos/sangue , Anticorpos/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Contagem de Células , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/efeitos dos fármacos , Imunoglobulina G/sangue , Imunoglobulina G/efeitos dos fármacos , Leucócitos/citologia , Masculino , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Pleura/citologia , Pleurisia/induzido quimicamente , Pleurisia/fisiopatologia , Ratos , Ratos Wistar , Substância P/metabolismoRESUMO
Chronic administration of the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats causes hypertension and morphological abnormalities in the heart, consisting mainly of ventricular hypertrophy and foci of necrosis and fibrosis. Since these phenomena have usually been described with high (or moderate) doses of L-NAME, this study was undertaken to evaluate the effects of a low dose of L-NAME on arterial blood pressure, heart weight index, left ventricular weight index, amount of ventricular fibrosis, and cardiomyocyte size. Male Wistar rats received L-NAME (7.5 mg/kg per day) in the drinking water for 2, 4, and 6 months, whereas control animals received tap water alone. At this dose, L-NAME caused 90% inhibition (P<0.001) of brain NO synthase (NOS) activity. The chronic L-NAME treatment caused an approximately 15% reduction in body weight of the animals, and no death was observed. The tail-cuff pressure was markedly (P<0.01) elevated in L-NAME-treated rats. A significant (P<0.05) reduction in both heart weight index (13-20% decrease) and left ventricular weight index (20-34% decrease) at 2, 4, and 6 months of treatment was observed in L-NAME-treated rats. The cardiomyocyte size in subendocardial, subepicardial, and midmyocardial regions of the left ventricles was time-dependently reduced, irrespective of the region studied, as measured at 2 (11% decrease), 4 (28% decrease, P<0.05), and 6 (45% decrease, P<0.05) months of chronic L-NAME treatment. The amount of fibrous tissue was unaltered at 2 and 4 months, but a small (but significant) increase in the amount of fibrous tissue was detected at 6 months (7.1+/-0.2 %, P<0.05) compared to that of control animals (5.9+/-0.2%). Our results show that chronic treatment of rats with a low dose of L-NAME for prolonged periods (up to 6 months) causes arterial hypertension accompanied by significant reductions in heart weight, left ventricular weight indexes, and cardiomyocyte size.
Assuntos
Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Inibidores Enzimáticos/toxicidade , Miocárdio/patologia , NG-Nitroarginina Metil Éster/toxicidade , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Fibrose/induzido quimicamente , Fibrose/patologia , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/patologia , Masculino , Miocárdio/ultraestrutura , Óxido Nítrico Sintase Tipo I , Óxido Nítrico Sintase Tipo III , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The influence of nitric oxide (NO) on eosinophil infiltration into the airways was investigated in rats actively sensitized with ovalbumin. The animals were treated chronically with the NO synthase inhibitor, N omega-Nitro-L-arginine methyl ester (L-NAME; 75 mumol rat-1 day-1), for 4 weeks. Bronchoalveolar lavage was performed at 6, 24, 48 and 72 h after intratracheal injection of ovalbumin. Intratracheal challenge of the sensitized rats with ovalbumin caused a significant increase in total leucocyte infiltration in bronchoalveolar lavage fluid both 24 and 48 h post-ovalbumin injection. Neutrophils and eosinophils peaked, respectively, at 24 h (29%) and 48 h (30%) in bronchoalveolar lavage fluid whereas the mononuclear cell did not differ significantly from the counts in non-sensitized rats at any time. At both 6 and 24 h post-ovalbumin injection, the chronic treatment of the animals with L-NAME affected neither the total nor the differential leucocyte content. However, at 48 h post-ovalbumin challenge, the total cell count was reduced by approximately 48% in the L-NAME-treated animals and this was associated with a marked inhibition (81%) of the eosinophil influx. Histological examination of the lungs from these animals (48 h post-ovalbumin challenge) also showed a prominent reduction (69.5%; P < 0.05) of the eosinophil infiltration in the respiratory segments. Our results demonstrate that NO plays a pivotal role in the eosinophil infiltration in airways of actively sensitized rats.
Assuntos
Asma/fisiopatologia , Inibidores Enzimáticos/farmacologia , Eosinófilos/patologia , Óxido Nítrico/fisiologia , Ovalbumina/farmacologia , Animais , Asma/induzido quimicamente , Asma/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Inibidores Enzimáticos/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Histocitoquímica , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Ovalbumina/imunologia , Ratos , Ratos WistarRESUMO
The effects of the Ca2+ channel blockers diltiazem, nifedipine and amlodipine were investigated on both arterial hypertension and myocardial changes induced by chronic blockade of nitric oxide synthesis. Control male Wistar rats received Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg rat(-1) day(-1)) in the drinking water for 8 weeks; blood pressure and body weight were monitored weekly. The Ca2+ channel blockers were given concomitantly to L-NAME, as follows: diltiazem (13.5 mg rat(-1) day(-1)) and amlodipine (6.25 mg rat(-1) day(-1)) were administered in the drinking water whereas nifedipine (6.25 mg rat(-1) day(-1)) was given in the chow. Nomega-nitro-L-arginine methyl ester induced a time-dependent increase in blood pressure which was significantly attenuated by diltiazem (154+/-1.6 vs. 139+/-1.6 mm Hg, p < 0.05), nifedipine (166+/-2.7 vs. 150+/-2.1 mm Hg, p < 0.05) and amlodipine (208+/-5.8 vs. 158+/-1.8 mm Hg, p < 0.05) at the last week of the treatment. Rats treated with the L-NAME also developed myocardial ischaemia, as indicated by the increased percentage of fibrous tissue found in the left ventricles of these animals (10.9+/-0.1%, p < 0.01) when compared to control ones (6.3+/-0.1%). Neither diltiazem (14.9+/-1.2%) nor nifedipine (11.1+/-1.5%) prevented this effect whereas amlodipine (6.9+/-1.1%, p < 0.01) virtually abolished the increase in fibrous tissue induced by L-NAME. The plasma concentration of the Ca2+ channel blockers was measured by liquid chromatography coupled to mass spectrometry at two different time points (morning and afternoon). Only amlodipine treatment was able to maintain constant levels (186+/-46 ng ml(-1) in the morning and 110+/-19 ng ml(-1) in the evening) compared to nifedipine (3003+/-578 ng ml(-1) in the morning and 436+/-100 ng ml(-1) in the evening) and diltiazem (77+/-51 ng ml(-1) in the morning and not detectable in the evening). In conclusion, our results indicate that amlodipine (but not diltiazem and nifedipine) can efficiently control myocardial ischaemia in nitric oxide deficient rats, probably due to its intrinsically long half-life.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Hipertensão/prevenção & controle , Isquemia Miocárdica/prevenção & controle , Óxido Nítrico/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial/métodos , Peso Corporal/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/sangue , Diltiazem/sangue , Diltiazem/farmacologia , Inibidores Enzimáticos/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , NG-Nitroarginina Metil Éster/farmacologia , Nifedipino/sangue , Nifedipino/farmacologia , Ratos , Ratos Wistar , Análise de SobrevidaRESUMO
Pravastatin is useful in restoring endothelium-dependent relaxation in hypercholesterolemic animals. A single intravenous bolus injection of N(omega)-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthase, causes myocardial necrosis and reduces coronary flow in rats. Since rats do not develop hypercholesterolemia and atherosclerosis, we have tested the hypothesis that pravastatin protects the heart from myocardial lesions induced by L-NAME in the absence of alterations in cholesterol levels and plaque formation. Male Wistar rats fed standard chow were divided into four groups: CONTROL (n=14) - rats that received tap water alone for 18 days; L-NAME (n=14) -- rats that received L-NAME (15 mg/kg, i.v.) on the 14th day of the study; PRAVASTATIN (n=11) -- rats that received pravastatin (6 mg/kg/day) in their drinking water for 18 days; PRAVASTATIN+L-NAME (n=12) -- rats that received pravastatin (6 mg/kg/day) and L-NAME (15 mg/kg, i.v.) as indicated in the preceding groups. At the end of 18 days, the rats were sacrificed and the hearts removed for stereological analysis by light microscopy. Plasma nitrate/nitrite and thromboxane B(2) concentrations were determined immediately before and after L-NAME administration. Pravastatin prevented the ischemic lesions induced by the acute inhibition of NO biosynthesis (the area of myocardial lesions in the L-NAME group was greater than in the Pravastatin+L-NAME group: 101.6 microm(2) vs. 1.2 microm(2), respectively; P<0.0001) and markedly increased the plasma nitrate/nitrate concentrations, even before L-NAME administration. There were no significant changes in the plasma thromboxane B(2) concentrations.
Assuntos
Anticolesterolemiantes/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Óxido Nítrico Sintase/biossíntese , Pravastatina/uso terapêutico , Análise de Variância , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos , Masculino , NG-Nitroarginina Metil Éster , Necrose , Nitratos/sangue , Nitritos/sangue , Ratos , Ratos Wistar , Tromboxano B2/sangueRESUMO
Excessive alcohol consumption causes metabolic changes and pathologic alterations in testes and accessory sex organ in different animal species. The aim of the present study was to evaluate the macroscopic, histologic and ultrastructural alterations provoked by chronic ingestion of different ethanol concentrations over increasing periods of time on the secretory epithelium of the seminal vesicle of C57/BL/6J mice in using stereological methods. Sixty male adult mice were divided into three experimental groups: Control, Alcoholic 25% and Alcoholic 35%, respectively, receiving tap water and tap water containing ethanol diluted to 25 and 35 degrees Gay Lussac. All mice were fed with the same solid diet. After 150 and 250 days of treatment the animals were sacrificed and the seminal vesicles were collected and processed for light and transmission electron microscopy. The cellular, cytoplasmic and nuclear volumes and the area density of autophagic and secretory vacuoles were measured. The histologic alterations observed in the alcoholic mice consisted of a reduction in epithelial size and cell volume, with maintenance of the same nuclear and cytoplasmic ratio as verified in the control groups. The ultrastructural alterations were: increased density of dense body area, decreased density of secretory granule area, and dilated rough endoplasmic reticulum and Golgi cisternae. We conclude that chronic ethanol ingestion causes depleting morphologic alterations in the epithelial cells of the seminal vesicle and negatively affects the secretory process of this gland.
Assuntos
Alcoolismo/patologia , Células Epiteliais/efeitos dos fármacos , Glândulas Seminais/efeitos dos fármacos , Alcoolismo/fisiopatologia , Animais , Peso Corporal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/toxicidade , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Etanol/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Glândulas Seminais/patologia , Glândulas Seminais/ultraestrutura , Vacúolos/patologia , Vacúolos/ultraestruturaRESUMO
This study reports on the usefulness of skin mast cell quantification (mast cells(mm2) as a parameter for the diagnosis of atopic dermatitis (AD) and for determining the efficacy of the therapeutic measures employed. Fifteen children with AD of moderate to extreme severity, and which started within the first two years of life, were studied. The therapeutic measures were limited to advice regarding the choice of adequate living conditions and of an appropriate diet in conjunction with the oral administration of hydroxyzine. Before treatment, 11 children with active AD were submitted to biopsies of both affected and non-affected skin. After treatment, in six children who were asymptomatic for at least one month, another biopsy was performed at a site of previous skin disease. A biopsy of a previously affected site was also performed in the other four children with a personal history of AD and who had no symptoms for more than one year. Treatment with hydroxyzine significantly reduced the number of papillar and reticular mast cells/mm3 of affected skin. In children who had been asymptomatic for one month, the number of papillar dermis mast cells/mm3 was greater than in those who had been asymptomatic for 12 months. In both groups of asymptomatic children, the number of mast cells/mm3 of affected skin was greater than in non-affected skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Dermatite Atópica/patologia , Mastócitos , Biópsia , Contagem de Células , Criança , Pré-Escolar , Dermatite Atópica/diagnóstico , Dermatite Atópica/dietoterapia , Dermatite Atópica/tratamento farmacológico , Avaliação de Medicamentos/métodos , Meio Ambiente , Feminino , Humanos , Hidroxizina/uso terapêutico , Lactente , MasculinoRESUMO
As nadadeiras dos teleósteos säo constituídas por unidades esqueléticas segmentares denominadas lepidotriquiais ou raios. Essas nadadeiras estäo envolvidas em processos regenerativos: assim, o conhecimento de sua estruturaçäo normal é de fundamental importância tanto para a compreensäo do processo de crescimento como de sua regeneraçäo. Com o objetivo de detectar substâncias lipídicas, as nadadeiras caudais foram fixadas pela formalina contendo bicloreto de cálcio a 3 por cento por 24 horas, à temperatura ambiente. Cortes com 10um de espessura, obtidos em micrótomo de congelaçäo foram submetidos às seguintes reaçöes histoquímicas específicas para lipídios: 1) Permanganato de Potássio Alcalino - Azul de Toluidina, para detecçäo de vitamina D; 2) Acido Perfórmico-Azul de Toluidina, para detecçäo de vitamina E e 3) Acido Peracético-Azul de Toluidina, para detecçäo de colesterol. Os controles para os testes histoquímicos 1, 2 e 3 foram feitos omitindo-se o agente oxidante. Reaçöes positivas obtidas para as reaçöes 1, 2 e 3 demonstraram a presença de vitamina D, E e colesterol nos raios das nadadeiras caudais da espécie Tilapia rendalli