RESUMEN
Background: Mitochondrial activity is essential for cardiac and skeletal muscle. The relationship between mitochondrial dysfunction and different cardiovascular conditions has been well described. Pharmacological treatment for heart failure involves different drugs as: angiotensin-converting enzyme inhibitors, B-adrenergic blockers, digitalis glycosides and diuretics. The clinical benefit from medication is clear, however, the role of this drugs in mitochondrial metabolisms is not well understood. Aim of the study: The objective of our study was to analyze structural and functional characteristics of cardiac and skeletal muscle mitochondria in mice treated with drugs normally used for heart failure and compare it to a control group. Methods: Twenty-five Albino Mice divided in five groups were treated with heart failure medication during 30 days (group I to IV). 30 days after treatment they were sacrificed, heart and skeletal muscle were analyzed and compared with a control group (V). Results: Enzymatic activity was slightly increased in groups treated with heart failure medication compared to control group (p>0.05). Mitochondrial morphology was significantly altered in groups treated compared to control group, in addition, mitochondrial area was significantly increased in the treated groups, in both cardiac and skeletal muscle. Conclusions: We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology. Methods: Twenty-five Albino Mice divided in five groups were treated with heart failure medication during 30 days (group I to IV). 30 days after treatment they were sacrificed, heart and skeletal muscle were analyzed and compared with a control group (V). Results: Enzymatic activity was slightly increased in groups treated with heart failure medication compared to control group (p>0.05). Mitochondrial morphology was significantly altered in groups treated compared to control group, in addition, mitochondrial area was significantly increased in the treated groups, in both cardiac and skeletal muscle. Conclusions: We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology. Results: Enzymatic activity was slightly increased in groups treated with heart failure medication compared to control group (p>0.05). Mitochondrial morphology was significantly altered in groups treated compared to control group, in addition, mitochondrial area was significantly increased in the treated groups, in both cardiac and skeletal muscle. Conclusions: We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology. Conclusions: We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology.
Introducción: la actividad mitocondrial es esencial para el músculo cardíaco y esquelético. La relación entre la disfunción mitocondrial y diferentes condiciones cardiovasculares ha sido bien descrita. El tratamiento farmacológico de la insuficiencia cardíaca implica diferentes medicamentos como: inhibidores de la enzima convertidora de la angiotensina, bloqueadores B-adrenérgicos, glucósidos digitálicos y diuréticos. Los beneficios clínicos del tratamiento son claros, sin embargo, el papel de estos fármacos en el metabolismo mitocondrial no esta bien establecido.Objetivo del estudio: El objetivo de nuestro estudio fue analizar las características estructurales y funcionales de las mitocondrias del músculo cardíaco y esquelético en ratones tratados con fármacos habitualmente utilizados para la insuficiencia cardíaca y compararlo con un grupo control.Métodos: Veinticinco ratones albinos divididos en cinco grupos fueron tratados con la medicación para insuficiencia cardíaca durante 30 días (grupo I a IV). 30 días después del tratamiento se sacrificaron, el corazón y el músculo esquelético se analizaron y se compararon con un grupo control (V).Resultados: La actividad enzimática se incrementó ligeramente en los grupos tratados con medicamentos insuficiencia cardiaca en comparación con el grupo control (p> 0,05). morfología mitocondrial se modificó significativamente en los grupos tratados en comparación con el grupo control, además, el área mitocondrial fue significativamente mayor en los grupos tratados, tanto en el músculo cardíaco y estriado.Conclusiones: Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología. Objetivo: El objetivo de nuestro estudio fue analizar las características estructurales y funcionales de las mitocondrias del músculo cardíaco y esquelético en ratones tratados con fármacos habitualmente utilizados para la insuficiencia cardíaca y compararlo con un grupo control. Métodos: Veinticinco ratones albinos divididos en cinco grupos fueron tratados con la medicación para insuficiencia cardíaca durante 30 días (grupo I a IV). 30 días después del tratamiento se sacrificaron, el corazón y el músculo esquelético se analizaron y se compararon con un grupo control (V).Resultados: La actividad enzimática se incrementó ligeramente en los grupos tratados con medicamentos insuficiencia cardiaca en comparación con el grupo control (p> 0,05). morfología mitocondrial se modificó significativamente en los grupos tratados en comparación con el grupo control, además, el área mitocondrial fue significativamente mayor en los grupos tratados, tanto en el músculo cardíaco y estriado.Conclusiones: Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología. Resultados: La actividad enzimática se incrementó ligeramente en los grupos tratados con medicamentos insuficiencia cardiaca en comparación con el grupo control (p> 0,05). morfología mitocondrial se modificó significativamente en los grupos tratados en comparación con el grupo control, además, el área mitocondrial fue significativamente mayor en los grupos tratados, tanto en el músculo cardíaco y estriado.Conclusiones: Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología. Conclusiones: Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología.
Asunto(s)
Antihipertensivos/uso terapéutico , Cardiotónicos/farmacología , Diuréticos/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Dinitrato de Isosorbide/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Animales , Antihipertensivos/farmacología , Atenolol/farmacología , Digoxina/farmacología , Modelos Animales de Enfermedad , Electrocardiografía , Enalapril/farmacología , Femenino , Furosemida/farmacología , Insuficiencia Cardíaca/fisiopatología , Masculino , Ratones , Mitocondrias Cardíacas/fisiología , Mitocondrias Cardíacas/ultraestructura , Espironolactona/farmacologíaRESUMEN
The purpose of this study was to develop a reservoir-type transdermal delivery system for isosorbide dinitrate (ISDN). The developed patch consisted of five layers from bottom to top, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing. The effects of chemical penetration enhancers, reservoir materials and rate-controlling membranes on the release behaviour of ISDN from the transdermal patch were studied, and the
O objetivo do presente estudo foi desenvolver um sistema de liberação transdérmico do tipo reservatório para o dinitrato de isossorbida (ISDN, abrevitura em Inglês). A formulação transdérmica desenvolvida constou de cinco camadas de baixo para cima, ou seja, um revestimento temporário, uma camada adesiva, uma membrana controladora da taxa de liberação, um reservatório e um reforço. Estudaram-se os efeitos dos potenciadores de penetração química, materiais do reservatório e membranas de controle da taxa de liberação no comportamento da formulação transdérmica de dinitrato de isossorbida. A liberação
Asunto(s)
Humanos , Dinitrato de Isosorbide/administración & dosificación , Dinitrato de Isosorbide/análisis , Dinitrato de Isosorbide/farmacocinética , Dinitrato de Isosorbide/farmacología , Administración Cutánea , Angina de Pecho/tratamiento farmacológico , Química Farmacéutica , PermeabilidadRESUMEN
BACKGROUND: it has been suggested that nitric oxide generators, such as isosorbide dinitrate, may be an alternative to mimic the effects of signal transduction mechanisms leading to cervical ripening, without affecting uterine contractility. OBJECTIVE: to compare the isosorbide dinitrate and dinoprostone for induction of labor in term pregnancy. MATERIAL AND METHODS: in a randomized controlled blinded clinical trial, we studied 66 patients divided into 2 groups: 33 patients were given 20 mg of isosorbide dinitrate and to the other 33 were administered 0.5 mcg of dinoprostone; in both groups the drugs were administered vaginally each 6 h and at maximum 3 times. It was carried out a cardiotocographic study in order to determine the presence or absence of uterine activity and to exclude disorders of the fetal heart frequency; it was performed a vaginal examination to assess cervical conditions determining the Bishop score at 0, 6 and 12 h. RESULTS: there were no differences between the groups in the determinations of mean arterial pressure, maternal heart frequency, fetal heart frequency and Bishop score registered at 6 y 12 h followed the drugs administration. The time of delivery was 20.7 +/- 1.8 h in the group of women treated with dinoprostone; and 16.3 +/- 1.4 h in women treated with isosorbide dinitrate (p=0.032). The cost was higher in women treated with dinoprostone ($560 vs $12, respectively, p=0.001). There was no difference between the groups related to: frequency of meconium stained liquid (p=1.000), mode of delivery by caesarean section (p=0.918), Apgar score at 1 minute (p=0.764) and 5 minutes (p=0.294) and mother discharged with healthy baby (p=1.000). CONCLUSIONS: the isosorbide dinitrate is associated with lower duration of labor compared with dinoprostone. There was no difference in the maternal-fetal outcome by using whatever drug.
Asunto(s)
Dinoprostona , Dinitrato de Isosorbide , Oxitócicos , Administración Intravaginal , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Dinoprostona/administración & dosificación , Dinoprostona/economía , Dinoprostona/farmacología , Método Doble Ciego , Femenino , Corazón Fetal/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Recién Nacido , Dinitrato de Isosorbide/administración & dosificación , Dinitrato de Isosorbide/economía , Dinitrato de Isosorbide/farmacología , Trabajo de Parto Inducido , Oxitócicos/administración & dosificación , Oxitócicos/economía , Oxitócicos/farmacología , Embarazo , Resultado del Embarazo , Tercer Trimestre del Embarazo , Adulto JovenRESUMEN
OBJETIVO: Avaliar o efeito do dinitrato de isossorbida (DNI) sobre a hiperalgesia corneana e a infiltração de neutrófilos em um modelo experimental de ceratite superficial induzida pelo lipopolissacarídeo (LPS). MÉTODOS: A hiperalgesia foi estudada através da indução de uma ceratite inflamatória em ratos (n = 60), pela exposição da córnea ao LPS (LPS +). Após a exposição, os olhos foram tratados durante quatro dias, com as soluções tópicas: DNI (200 mg, 65 mg e 20 mg), prednisolona 1 por cento (PRED) ou Veículo. Olhos controles foram expostos apenas à solução salina (LPS -). Para avaliar a dor ocular, contouse o número de piscadas em 40 segundos, após instilação de uma gota de capsaicina 0,01 mM. A análise histopatológica foi realizada para avaliação da infiltração neutrofílica. RESULTADOS: Foram observadas áreas esbranquiçadas no estroma corneano dos olhos com a ceratite induzida pelo LPS, entre os dias 3 e 15 dias. Esses olhos (LPS +) apresentaram um número significativamente maior de piscadas que os LPS - (P = 0,019) à estimulação química. O tratamento tópico com o DNI reduziu o número de piscadas observadas (P = 0,010). Da mesma forma, olhos expostos ao LPS e tratados com DNI demonstraram redução significativa na infiltração neutrofílica (P = 0,0031). CONCLUSÃO: Baixas doses de DNI reduziram a hiperalgesia corneana e a infiltração neutrofílica nesse modelo de ceratite. Dessa forma, doadores de óxido nítrico, como o DNI, poderão ser úteis no futuro ao tratamento clínico de diversas condições dolorosas da superfície ocular.
PURPOSE: To analyze effects of isosorbide dinitrate (DNI) on corneal hyperalgesia and neutrophil infiltration in an experimental model of superficial keratitis induced by lipopolysaccharide (LPS). METHODS: Hyperalgesia was studied through the induction of inflammatory keratitis in rats (n=60), by corneal exposure to LPS. Following exposure, the inflamed eye was treated for four days, with one of the following solutions: topical DNI (200 λg, 65 λg and 20 λg), prednisolone 1 percent (PRED), and vehicle. Saline-exposed eyes (LPS -) underwent the same protocol. To evaluate ocular pain, the number of blinks in 40 seconds was counted, after one drop of 0.01 λM capsaicin. Histopathological analysis was performed with evaluation of neutrophil infiltration. RESULTS: White clouding areas were observed in the corneal stroma of eyes with LPS-induced keratitis, between day 3 and day 15. Eyes exposed to LPS had a significantly higher number of blinks than LPS - (P=0.019). Topical treatment of LPS-induced keratitis eyes with DNI reduced capsaicin-induced blinks (P=0.010). Similarly, eyes exposed to LPS and treated with DNI also displayed reduced neutrophil infiltration (P=0.0031). CONCLUSION: Low doses of topical NO donors, like DNI, reduce corneal hyperalgesia and neutrophil infiltration in this keratitis model. NO donors may be useful in the clinical treatment of painful conditions associated with surgical procedures of the ocular surface.
Asunto(s)
Animales , Lipopolisacáridos/toxicidad , Hiperalgesia/tratamiento farmacológico , Dinitrato de Isosorbide/administración & dosificación , Queratitis/inducido químicamente , Lipopolisacáridos/administración & dosificación , Ratas Wistar , Córnea/efectos de los fármacos , Córnea/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hiperalgesia/metabolismo , Dinitrato de Isosorbide/farmacología , Queratitis/patologíaRESUMEN
BACKGROUND: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent. AIM: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment. METHODS: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration. RESULTS: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared to each other. CONCLUSION: Isosorbide dinitrate has a cytoprotective activity on the gastric mucosa of rats submitted to ketoprofen action.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Mucosa Gástrica/efectos de los fármacos , Dinitrato de Isosorbide/farmacología , Cetoprofeno/efectos adversos , Donantes de Óxido Nítrico/farmacología , Úlcera Gástrica/prevención & control , Animales , Modelos Animales de Enfermedad , Masculino , Malondialdehído/análisis , Ratas , Ratas Wistar , Estadísticas no Paramétricas , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
BACKGROUND: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent. AIM: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment. METHODS: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration. RESULTS: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared...
RACIONAL: Drogas antiinflamatórias não-esteróides são consideradas, atualmente, importante grupo de medicamentos, com ampla variedade de uso terapêutico, em diferentes áreas da medicina moderna. Apesar de seus efeitos benéficos para o paciente, apresentam grande incidência de efeitos colaterais, principalmente no trato gastrointestinal. Os mecanismos fisiopatológicos de lesões induzidas por essas drogas e os mecanismos de defesa da mucosa gástrica tornaram-se uma importante linha de pesquisa médica, especialmente procurando avaliar o papel de óxido nítrico como agente citoprotetor. OBJETIVO: Estudar uma droga doadora de ácido nítrico - o dinitrato de isossorbida - e sua ação citoprotetora da mucosa gástrica de ratos submetidos ao tratamento com uma droga antiinflamatória - o cetoprofeno. MÉTODOS: Ratos machos adultos previamente submetidos a jejum de 24 horas, foram divididos em três grupos: a) grupo I (controle): animais, que receberam apenas solução salina isotônica via intragástrica, por gavagem e via endovenosa; b) grupo II (cetoprofeno-controle): animais que receberam solução salina via intragástrica por gavagem e cetoprofeno via endovenosa, e c) grupo III (nitrato/cetoprofeno): animais que receberam solução de 2 mM de dinitrato de isossorbida a via intragástrica por gavagem e cetoprofeno via endovenosa. Esses grupos foram, posteriormente, submetidos a exames macroscópico, microscópico e bioquímico, avaliando-se os seguintes parâmetros: a) determinação do índice de lesão gástrica; b) determinação da espessura da camada do muco secretor; c) determinação da concentração de ácido nítrico x tecidual, e d) determinação da concentração do malondialdeído tecidual. RESULTADOS: Encontrou-se menor índice de lesão gástrica nos animais do grupo III (nitrato), assim como maior espessura da camada do muco secretor nos animais deste grupo, do que nos animais do grupo II (cetoprofeno). A variação da concentração do ácido nítrico x tecidual foi semelhante nos três grupos. A taxa...
Asunto(s)
Animales , Masculino , Ratas , Antiinflamatorios no Esteroideos/toxicidad , Mucosa Gástrica/efectos de los fármacos , Dinitrato de Isosorbide/uso terapéutico , Cetoprofeno/toxicidad , Donantes de Óxido Nítrico/uso terapéutico , Úlcera Gástrica/prevención & control , Modelos Animales de Enfermedad , Mucosa Gástrica/patología , Dinitrato de Isosorbide/farmacología , Malondialdehído/análogos & derivados , Donantes de Óxido Nítrico/farmacología , Ratas Wistar , Estadísticas no Paramétricas , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
BACKGROUND AND PURPOSE: Andean highlanders, unlike Ethiopians, develop chronic mountain sickness (CMS), a maladaptation to their native land. Ambient hypoxia induces NO-mediated vasodilatation. Fitness for life at altitude might be revealed by cerebrovascular responses to NO. METHODS: Nine altitude-native men were examined at 3622 and 794 m in Ethiopia and compared with 9 altitude-native Andean men tested at 4338 and 150 m in Peru. We assessed CMS scores, hematocrits, end-tidal pressure of carbon dioxide (P(ET)co2), oxygen saturations, and cerebral blood flow velocity (CBV). We evaluated fitness for life at altitude from the cerebrovascular response to an exogenous NO donor. RESULTS: At high altitude, CMS scores and hematocrits were higher in Andeans, and they had lower oxygen saturations. Ethiopians had higher P(ET)co2 at all study sites. At low altitude, saturations were similar in both groups. Responsiveness of the cerebral circulation to NO was minimal in Ethiopians at low altitude, whereas Andeans had a large response. In contrast, at high altitude, Ethiopians showed large responses, and Peruvians had minimal responses. CONCLUSIONS: By our measure, high altitude-native Peruvians were well-adapted lowlanders, whereas Ethiopian highlanders were well adapted to altitude life. Environmental pressures were sufficient for human adaptation to chronic hypoxia in Africa but not South America. The mechanisms underlying these differences are unknown, although studies of neurovascular diseases suggest that this may be related to a NO receptor polymorphism.
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Aclimatación/fisiología , Mal de Altura/fisiopatología , Población Negra , Circulación Cerebrovascular/efectos de los fármacos , Hipoxia Encefálica/fisiopatología , Indígenas Sudamericanos , Dinitrato de Isosorbide , Donantes de Óxido Nítrico , Nitroglicerina , Adulto , Mal de Altura/epidemiología , Mal de Altura/etnología , Población Negra/genética , Velocidad del Flujo Sanguíneo , Pruebas Respiratorias , Dióxido de Carbono/análisis , Etiopía/epidemiología , Hematócrito , Humanos , Hipoxia Encefálica/etnología , Hipoxia Encefálica/etiología , Indígenas Sudamericanos/genética , Dinitrato de Isosorbide/farmacología , Masculino , Óxido Nítrico/fisiología , Donantes de Óxido Nítrico/farmacología , Nitroglicerina/farmacología , Oxígeno/sangre , Perú/epidemiología , Perú/etnología , Aptitud Física , Selección GenéticaRESUMEN
It has been suggested that nigrostriatal dopaminergic transmission is modulated by nitric oxide (NO). Since there is evidence that gonadal hormones can affect extrapyramidal motor behavior in mammals, we investigated the effects of isosorbide dinitrate (ISD), linsidomine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP), three pharmacologically different NO donors, on neuroleptic-induced catalepsy in 60- to 80-day-old male and female albino mice. Catalepsy was induced with haloperidol (1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Drugs (or appropriate vehicle) were injected ip 30 min before haloperidol, with each animal being used only once. ISD (5, 20 and 50 mg/kg) caused a dose-dependent inhibition of catalepsy in male mice (maximal effect 120 min after haloperidol: 64% inhibition). In the females only at the highest dose of ISD was an attenuation of catalepsy observed, which was mild and short lasting. SIN-1 (10 and 50 mg/kg) did not significantly affect catalepsy in female mice, while a significant attenuation was observed in males at the dose of 50 mg/kg (maximal inhibition: 60%). SNAP (20 mg/kg) significantly attenuated catalepsy in males 120 min after haloperidol (44% inhibition), but had no significant effect on females. These results basically agree with literature data showing that NO facilitates central dopaminergic transmission, although the mechanisms are not fully understood. They also reveal the existence of gender-related differences in this nitrergic modulation in mice, with females being less affected than males.
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Catalepsia/tratamiento farmacológico , Molsidomina/análogos & derivados , Donantes de Óxido Nítrico/farmacología , Análisis de Varianza , Animales , Antipsicóticos , Catalepsia/inducido químicamente , Femenino , Haloperidol , Dinitrato de Isosorbide/farmacología , Masculino , Ratones , Molsidomina/farmacología , S-Nitroso-N-Acetilpenicilamina/farmacología , Factores SexualesRESUMEN
The nitric oxide (NO) has important participation in the control of hypothalamic-pituitary axis. The authors investigated the effect of NO donor, isosorbide dinitrate (ISDN), on prolactin (PRL) release induced by immobilization stress (IS) in male rats. Pretreatment with the NO donor, ISDN (2.5; 5 and 10 mg/kg), inhibited about 60-85% of the PRL response to IS. It is concluded that NO does participate in the regulation of PRL response to IS.
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Óxido Nítrico/fisiología , Prolactina/metabolismo , Estrés Psicológico/metabolismo , Animales , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Dinitrato de Isosorbide/farmacología , Masculino , Donantes de Óxido Nítrico/farmacología , Prolactina/sangre , Ratas , Ratas Wistar , Restricción Física , Estrés Psicológico/sangreRESUMEN
BACKGROUND/AIMS: In patients with cirrhosis pharmacological treatment of portal hypertension using beta-blockers and vasodilators has raised concerns for its potential deleterious effects on renal function and encephalopathy. To clarify this issue we evaluated the effects of propranolol and 5-isosorbide mononitrate or both on subclinical hepatic encephalopathy and renal function in a prospective randomized double-blinded study. METHODOLOGY: Thirty patients Child-Pugh A or B, with esophageal varices, normal renal function and non-previous pharmacological treatment were studied. After a basal period, patients received during 4 weeks 5-isosorbide mononitrate (80 mg/day) or placebo. In the next 4 weeks, propranolol was added to both groups. At baseline and at the end of each study period we assessed: renal function tests; plasma renin activity and aldosterone; subclinical hepatic encephalopathy (electroencephalograms, visual evoked potentials and psychometric studies). Mean arterial pressure, cardiac output (echo-Doppler) and indocyanine green retention were also measured. RESULTS: The most common alterations at baseline were increased arterial ammonia levels (85%), abnormal indocyanine green retention (75%), abnormal trail making B (44%), decreased inulin clearance (30%) and high plasma renin activity (27%). After 4 weeks of 5-isosorbide mononitrate or placebo no significant changes were observed in any variable. Five out of 14 patients receiving 5-isosorbide mononitrate were withdrawn due to side effects. The addition of propranolol decreased significantly plasma renin activity in both groups and cardiac output in those receiving 5-isosorbide mononitrate but did not change other variables. CONCLUSIONS: In patients with compensated or slightly decompensated liver cirrhosis 5-isosorbide mononitrate, propranolol or the association of both did not produce detectable worsening of subclinical hepatic encephalopathy or renal function.
Asunto(s)
Dinitrato de Isosorbide/análogos & derivados , Dinitrato de Isosorbide/farmacología , Cirrosis Hepática/fisiopatología , Hígado/efectos de los fármacos , Vasodilatadores/farmacología , Anciano , Método Doble Ciego , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Dinitrato de Isosorbide/uso terapéutico , Hígado/fisiopatología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Propranolol/farmacología , Renina/sangre , Vasodilatadores/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate and compare the usefulness of cineventriculographies, before and after nitrate use, to technetium-99m sestamibi scintigraphy for the identification of myocardial ischemia. METHODS: Twenty-six patients were studied at basal conditions and 5 minutes after intravenous administration of isosorbide mononitrate (0.3 mg/kg), to evaluate the performance and regional wall motion of the left ventricle (LV). The results were compared too those obtained with technetium-99m sestamibi scintigraphy. RESULTS: Before nitrate, contrast ventriculography identified 30 normal segments, 62 hypokinetic segments, 28 dyskinetic segments, and 14 akinetic segments. After drug administration, 99 segments were normal, 11 hypokinetic, 11 dyskinetic, and 13 akinetic. Myocardial scintigraphy revealed 110 ischemic segments and 18 fibrotic segments (p < 0.005). After drug administration, the ventriculography showed increase in the velocity of circumferential fiber shortening (p = 0.0142), the ejection fraction (p = 0.0462), decrease in the end-systolic volume (p = 0.0031) and no change in end-diastolic volume. CONCLUSION: Contrast ventriculography using nitrate proved to be similar to perfusional myocardial scintigraphy in the identification of myocardial ischemia.
Asunto(s)
Dinitrato de Isosorbide/análogos & derivados , Isquemia Miocárdica/diagnóstico por imagen , Ventriculografía con Radionúclidos , Tecnecio Tc 99m Sestamibi , Vasodilatadores/farmacología , Femenino , Humanos , Dinitrato de Isosorbide/farmacología , Masculino , Función Ventricular Izquierda/fisiologíaRESUMEN
Drugs which influence 5-HTergic mechanisms can modify neuroleptic-induced catalepsy (NC) in rodents, a phenomenon produced by striatal dopamine (DA) receptor blockade. Previous research also suggests a role for endogenous nitric oxide (NO) in the modulation of striatal DAergic neurotransmission; in addition, NO seems to play a role in the 5-HT reuptake mechanism. It is known that clomipramine potentiates NC in mice, but the reported effects of selective 5-HT reuptake inhibitors (SSRIs) in this model are rather contradictory. We then decided to re-address this issue, investigating the effect of fluoxetine (FX), an SSRI, on NC. In view of the ubiquitous role of NO as a central neuromodulator, we also studied the effect of isosorbide dinitrate (ID), a centrally active NO donor, and how both drugs interact to affect the phenomenon of NC. Catalepsy was induced in male albino mice with haloperidol (H; 1 mg/kg, i.p.) and measured at 30-min interval by means of a bar test. Drugs (FX, ID and FX + ID) or saline (controls) were injected i.p. 30 min before H, with each animal used only once. FX (5 mg/kg) significantly reduced NC, with maximal attenuation (about 74%) occurring at 150 min after H. ID (5 mg/kg) also inhibited NC (150 min: 62% attenuation). The combined drugs (FX + ID group), however, caused a great potentiation of NC (4.7-fold at its maximum, at 90 min). The effect observed with ID is compatible with the hypothesis that NO increases DA release in the striatum. The attenuation of NC observed with FX may be due to a preferential net effect on the raphe somatodendritic synapse, where inhibitory 5-HT1A autoreceptors are operative. The enhancement of NC caused by combined administration of FX and ID suggests the presence of a pharmacodynamic interaction, whose mechanism, still unclear, may be related to a decrease in striatal DA release.
Asunto(s)
Catalepsia/inducido químicamente , Cuerpo Estriado/efectos de los fármacos , Fluoxetina/farmacología , Dinitrato de Isosorbide/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Vasodilatadores/farmacología , Animales , Combinación de Medicamentos , Interacciones Farmacológicas , Masculino , Ratones , Factores de TiempoRESUMEN
Drugs which influence 5-HTergic mechanisms can modify neuroleptic-induced catalepsy (NC) in rodents, a phenomenon produced by striatal dopamine (DA) receptor blockade. Previous research also suggests a role for endogenous nitric oxide (NO) in the modulation of striatal DAergic neurotransmission; in addition, NO seems to play a role in the 5-HT reuptake mechanism. It is known that clomipramine potentiates NC in mice, but the reported effects of selective 5-HT reuptake inhibitors(SSRIs) in this model are rather contradictory. We then decided to re-address this issue, investigating the effect of fluoxetine (FX), an SSRI, on NC. In view of the ubiquitous role of NO as a central neuromodulator, we also studied the effect of isosorbide dinitrate (ID), a centrally active NO donor, and how both drugs interact to effect the phenomenon of NC. Catalepsy was induced in male albino mice with haloperidol (H; 1 mg/kg, ip) and measured at 30-min interval by means of a bar test. Drugs (FX, ID and FX + ID) or saline (controls) were injected ip 30 min before H, with each animal used only once. FX (5 mg/kg) significantly reduced NC, with maximal attenuation (about 74 percent) occurring at 150 min after H. ID (5 mg/kg) also inhibited NC (150 min: 62 percent attenuation). The combined drugs (FX + ID group), however caused a great potentiation of NC (4.7-fold at its maximum, at 90 min). The effect observed with ID is compatible with the hypothesis that NO increases DA release in the striatum. The attenuation of NC observed with FX may be due to a preferential net effect oon the raphe somatodendritic synapse, where inhibitory 5-HT(1A) autoreceptors are operative. The enhancement of NC caused by combined administration of FX and ID suggests the presence of a pharmacodynamic interaction, whose mechanism, still unclear, may be related to a decrease in striatal DA release.
Asunto(s)
Animales , Masculino , Catalepsia/inducido químicamente , Cuerpo Estriado/efectos de los fármacos , Fluoxetina/farmacología , Dinitrato de Isosorbide/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Vasodilatadores/farmacología , Combinación de Medicamentos , Interacciones Farmacológicas , Ratones , Factores de TiempoRESUMEN
PURPOSE: To evaluate the effect of sublingual isosorbide-5 mononitrate (ISMN) and nitroglycerin (NTG) on luminal diameter of epicardial coronary arteries, mean arterial pressure and deleterious effects. METHODS: Fifty patients were submitted to cardiac catheterization and coronary arteriography, at baseline, and 5 min after sublingual administration of ISMN, group A (GA) or NTG, group B (GB). RESULTS: Reference vessel diameter increased in both groups, without statistical significance. In GA and GB, a decrease (1.66 mmHg) and an increase (0.79 mmHg) in mean arterial pressure, respectively, were demonstrated (p = 0.123). There were no deleterious effects with the use of these drugs. CONCLUSION: Sublingual ISMN is an alternative to administration of NTG during coronary arteriography, and represents a therapeutic alternative to ischemic heart disease treatment.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Cateterismo Cardíaco , Cineangiografía/métodos , Vasos Coronarios/efectos de los fármacos , Dinitrato de Isosorbide/análogos & derivados , Nitroglicerina/farmacología , Vasodilatadores/farmacología , Administración Sublingual , Femenino , Humanos , Dinitrato de Isosorbide/administración & dosificación , Dinitrato de Isosorbide/farmacología , Masculino , Persona de Mediana Edad , Nitroglicerina/administración & dosificación , Vasodilatadores/administración & dosificaciónRESUMEN
PURPOSE: To evaluate the acute effects of isosorbide mononitrate on circulation, cardiac function and left ventricular segmental motility in patients with isquemic heart disease due to coronary artery disease. METHODS: Twenty-four patients with ischemic heart disease, 10 women, with mean age of 58 years, were studied during cardiac catheterization, at baseline condition and 5min after intravenous infusion of 0.3mg/kg of isosorbide mononitrate. RESULTS: After infusion of isosorbide mononitrate there were significant reduction in mean right atrial pressure no mean pulmonary artery pressure (< 0.0001), left ventricular and diastolic pressure (p < 0.004), left ventricular systolic pressure (p < 0.002), maximum (p < 0.002) and mean (p < 0.008) aortic pressure, and left ventricular systolic volume (p < 0.004), as well as significant increase in the left ventricular ejection fraction (p < 0.001) and mean velocity of circunferential fibers shortening (p < 0.001). There was no significant modification of minimum aortic pressure, heart rate, cardiac output nor of left ventricular and diastolic volume. With respect of segmental motility of the left ventricle after medication, 38 kypokinetic segments normalized their motility, 4 akinetic segments remained intact, and of the 21 dyskinetic segments, 6 normalized, 8 became hypokinetic and 7 remained dyskinetic. CONCLUSION: Isosorbide mononitrate, when used as intravenous infusion, have a rapid and direct effect on systemic and pulmonary circulation, and improving segmental motility and left ventricular performance in patients with impaired left ventricular motility caused by ischemic heart disease.
Asunto(s)
Enfermedad de la Arteria Coronaria/fisiopatología , Hemodinámica/efectos de los fármacos , Dinitrato de Isosorbide/análogos & derivados , Isquemia Miocárdica/fisiopatología , Vasodilatadores/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Cardíaco , Cineangiografía , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Inyecciones Intravenosas , Dinitrato de Isosorbide/farmacología , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Función Ventricular Izquierda/efectos de los fármacosAsunto(s)
Dinitrato de Isosorbide/análogos & derivados , Isquemia Miocárdica/tratamiento farmacológico , Vasodilatadores/farmacología , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Dinitrato de Isosorbide/farmacología , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/fisiopatología , Reperfusión Miocárdica , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
The effect of isosorbide dinitrate (ISD) on gastroesophageal reflux and gastric emptying during the 24-min period following a liquid meal was studied in healthy volunteers, Chagas' disease patients with normal esophageal motility (CD-1 group), and Chagas' disease patients with esophageal dysmotility (CD-2 group) with dynamic scintigraphy. At random, on two separate days, the subjects received 5 mg isosorbide dinitrate or an identical-appearing placebo tablet, by the sublingual route, and ingested a liquid test meal containing [99mTc]phytate colloid before scintigraphic studies were performed. Gastroesophageal reflux episodes were more frequent (P = 0.016) and gastroesophageal reflux indexes were greater (P < 0.010) after isosorbide dinitrate than after placebo in CD-2 group (N = 15) but not in healthy volunteers (N = 14) or CD-1 group (N = 9); six of seven CD-2 patients presenting with gastroesophageal reflux after isosorbide dinitrate had abnormal clearance of refluxate. Gastric emptying was similar in healthy volunteers (N = 13), CD-1 patients (N = 6), and CD-2 patients (N = 13), and no effect of isosorbide dinitrate on it was detected in any of the groups. In separate studies, 5 mg isosorbide dinitrate reduced the lower esophageal pressure (P < 0.01) in seven CD-2 patients. These results indicate that ISD increases the tendency towards GER in CD-2 patients, but not in healthy volunteers or CD-1 patients. This effect is probably related to an exceedingly intense relaxation of the LES caused by ISD in CD-2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedad de Chagas/complicaciones , Reflujo Gastroesofágico/fisiopatología , Dinitrato de Isosorbide/farmacología , Adulto , Anciano , Unión Esofagogástrica/fisiopatología , Esófago/fisiopatología , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Reflujo Gastroesofágico/diagnóstico por imagen , Reflujo Gastroesofágico/etiología , Humanos , Masculino , Manometría , Persona de Mediana Edad , CintigrafíaRESUMEN
Os efeitos da cardiomiotomia cirúrgica e do dinitrato de isossorbitol sobre o esvaziamento esofagiano em 18 portadores de megaesôfago chagásico. O esvaziamento esofagiano foi medido três vezes em cada paciente: duas vezes antes e uma vez após a realizaçäo da cardiomiotomia; 5mg de dinitrato de isossorbitol foi administrado por via sublingual 5 minutos antes de um dos estudos pré-operatórios. Os resultados revelaram que o dinitrato de isossorbitol e a cardiomiotomia aceleram o esvaziamento esofagiano com intensidade semelhante, embora a cardiomiotomia determine completo esvaziamento do esôfago mais freqüentemente do que o dinitato de isossorbitol
Asunto(s)
Adulto , Persona de Mediana Edad , Humanos , Masculino , Femenino , Acalasia del Esófago/terapia , Enfermedad de Chagas/terapia , Vaciamiento Gástrico , Dinitrato de Isosorbide/administración & dosificación , Acalasia del Esófago/cirugía , Acalasia del Esófago/tratamiento farmacológico , Administración Sublingual , Protocolos Clínicos , Vaciamiento Gástrico , Dinitrato de Isosorbide/farmacología , Dinitrato de Isosorbide/uso terapéuticoRESUMEN
The effects of surgical cardiomyotomy and isosorbide dinitrate on esophageal emptying were compared in 18 patients with symptomatic chagasic megaesophagus. The esophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique, twice before and once 10-14 days after cardiomyotomy. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded one of the preoperative studies. Esophageal retention at the completion of the meal was significantly less (P < 0.01) after both isosorbide dinitrate and cardiomyotomy than after the preoperative study not preceded by any treatment. This difference persisted up to 10 minutes after the meal. The values measured in the isosorbide dinitrate-preceded study and after cardiomyotomy were not different (P > 0.10) even though esophageal retention at the completion of the meal was slightly less after cardiomyotomy than after isosorbide dinitrate. These results show that isosorbide dinitrate and cardiomyotomy cause similar enhancement of esophageal emptying in chagasic megaesophagus.
Asunto(s)
Cardias/cirugía , Enfermedad de Chagas/complicaciones , Acalasia del Esófago/terapia , Vaciamiento Gástrico , Dinitrato de Isosorbide/administración & dosificación , Administración Sublingual , Adulto , Anciano , Protocolos Clínicos , Acalasia del Esófago/tratamiento farmacológico , Acalasia del Esófago/etiología , Acalasia del Esófago/cirugía , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Humanos , Dinitrato de Isosorbide/farmacología , Dinitrato de Isosorbide/uso terapéutico , Masculino , Persona de Mediana EdadRESUMEN
Isosorbide 5-mononitrate reduces portal pressure in acute conditions. The aim of this work was to assess its effects and tolerance development after 30 days of use in alcoholic cirrhotic patients without history of variceal bleeding. Nine patients with portal hypertension (7 with esophageal varices) were studied. Hepatic and systemic hemodynamic parameters were measured in basal conditions, after one hour and after 30 days of treatment (40 mg b i d). One patient was lost from control at 2 weeks. In the total group, portal pressure decreased from 15.1 +/- 3.7 mm Hg to 12.1 +/- 5 at one hour and 11.3 +/- 5.5 mm Hg at 30 days (p < 0.002). In two patients, portal pressure was not modified. Portal blood flow increased significantly at one hour in the 7 responder patients. Hepatic blood flow (indocyanine green clearance) was not modified; thus, estimated hepatic resistance decreases in both periods. Intrinsic indocyanine green clearance (a measure of hepatic function) did not change in any period. Systemic blood pressure decreased and cardiac rate increased only after one hour. The fall in portal pressure did not correlate with changes in portal or hepatic blood flow. It is concluded that isosorbide 5-mononitrate decreased portal pressure in 7 out of nine patients, even after 30 days of treatment, without untoward effects over hepatic function or perfusion.