RESUMEN
Experiments on Wistar rats showed that single intraperitoneal injection nonselective NO-synthase inhibitor L-NAME in a dose of 50 mg/kg was followed by transient proteinuria and albuminuria. This effect was not reproduced by injection of ODQ, an inhibitor of intracellular effects of NO, and arginine, but D-NAME, an optical isomer of L-NAME not blocking NO-synthase, produced similar, though less pronounced effect. The degree of proteinuria and albuminuria increased in combined treatment with nitroarginine methyl esters and 1-deamino-arginine vasotocin or arginine vasopressin. Proteinuria during treatment with arginine derivatives attests to not only their effect on the charge of the filtration membrane, but also the participation of NO-dependent processes in the regulation of ultrafiltration in renal glomeruli.
Asunto(s)
Albúminas/biosíntesis , Riñón/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Albúminas/metabolismo , Albuminuria/metabolismo , Animales , Arginina Vasopresina/administración & dosificación , Arginina Vasopresina/farmacología , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Femenino , Glomérulos Renales/metabolismo , NG-Nitroarginina Metil Éster/administración & dosificación , NG-Nitroarginina Metil Éster/análogos & derivados , NG-Nitroarginina Metil Éster/farmacología , Nitroarginina/administración & dosificación , Nitroarginina/análogos & derivados , Nitroarginina/farmacología , Proteinuria/metabolismo , Ratas , Ratas Wistar , Vasotocina/administración & dosificación , Vasotocina/análogos & derivados , Vasotocina/farmacologíaRESUMEN
Turtles (Chrysemys picta) were given the nitric oxide synthase inhibitor NW-nitro-L-arginine methyl ester (L-NAME) or its inactive isomer NW-nitro-D-arginine methyl ester (D-NAME) and were trained on a negative patterning task or a simple go/no-go discrimination task. L-NAME impaired the learning of negative patterning but did not affect retention of the task if it had already been learned. D-NAME had no effect. Go/no-go discrimination learning was not affected by L-NAME. These findings support the notion that nitric oxide plays a role in complex configural learning in a reptile closely related to the ancestors of mammals.
Asunto(s)
Aprendizaje/fisiología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/antagonistas & inhibidores , Tortugas/fisiología , Animales , Conducta Animal , Conducta de Elección/efectos de los fármacos , Conducta de Elección/fisiología , Aprendizaje Discriminativo/efectos de los fármacos , Aprendizaje Discriminativo/fisiología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Aprendizaje/efectos de los fármacos , NG-Nitroarginina Metil Éster/análogos & derivados , Probabilidad , Factores de TiempoRESUMEN
UNLABELLED: We investigated the vascular endothelial growth factor (VEGF) receptor [fms-like-tyrosine kinase (Flt-1 and fetal liver kinase-1 (Flk-1)] response to acute exercise. In female Wistar rats, the VEGF receptor messenger RNA (mRNA) response to a single acute exercise bout was examined using semi-quantitative Northern blot from the left gastrocnemius muscles at rest and post-exercise at 0, 1, 2, 4, 8, 16, 24 and 48 h. Exercise altered both Flt-1 and Flk-1 mRNA, with significant increases in Flt-1 mRNA at 1 and 24 h. However, post-hoc analysis was unable to discern the time point where a significant increase in Flk-1 mRNA occurred. To investigate the regulation of Flt-1 mRNA by exercise we examined if nitric oxide synthase (NOS) inhibition alters the Flt-1 mRNA response. Eight groups [ CONDITION: Rest or Exercise; Drug: Saline, 30 mg kg(-1)N(omega)-nitro-L-arginine methyl ester (L-NAME), 300 mg kg(-1) L-NAME or 300 mg kg(-1) D-NAME] were used to determine the effect of NOS inhibition on the Flt-1 mRNA response to exercise. L-NAME, a known NOS inhibitor, attenuated the exercise-induced increase in Flt-1 mRNA by approximately 50%. These findings suggest that: (1) exercise alters Flt-1 and Flk-1 gene expression; and (2) NO is important in the regulation of the Flt-1 gene response to exercise.
Asunto(s)
Proteínas de la Matriz Extracelular/genética , Músculo Esquelético/fisiología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Esfuerzo Físico/fisiología , Animales , Factores de Crecimiento Endotelial , Inhibidores Enzimáticos/farmacología , Proteínas de la Matriz Extracelular/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Péptidos y Proteínas de Señalización Intercelular , Linfocinas , NG-Nitroarginina Metil Éster/análogos & derivados , NG-Nitroarginina Metil Éster/farmacología , ARN Mensajero/metabolismo , ARN Ribosómico 18S/genética , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factor A de Crecimiento Endotelial Vascular , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Factores de Crecimiento Endotelial VascularRESUMEN
This study is the first to demonstrate activation of NF-kappaB binding just 10 minutes into the commonly employed hepatocyte isolation procedure. It is further reported that the anti-oxidant Trolox can prevent the induction of NF-kappaB during the well established hepatocyte isolation procedure but not during their subsequent culture. However both phases of NF-kappaB activation are inhibited by L-NAME intimating a role for NO production, via nitric oxide synthase. These findings demonstrate that at least 2 different signal transduction pathways are operative during hepatocyte isolation and culture. Thus further studies employing Trolox and L-NAME will help delineate how each pathway contributes to the generalised loss of liver function commonly observed in vitro.
Asunto(s)
Separación Celular , Hígado/citología , FN-kappa B/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/metabolismo , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Unión Competitiva , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromanos/farmacología , Ditiotreitol/farmacología , Inhibidores Enzimáticos/farmacología , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , FN-kappa B/antagonistas & inhibidores , NG-Nitroarginina Metil Éster/análogos & derivados , Nitratos/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Oligonucleótidos/genética , Oligonucleótidos/metabolismo , Unión Proteica/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Elementos de Respuesta/genética , Factores de TiempoRESUMEN
Duodenal mucosal alkaline secretion increases in response to hydrochloric acid exposure. The tentative role of nitric oxide (NO) in the mediation of this response was investigated. The mucosal alkaline output by a duodenal segment was recorded by in situ titration in chloralose-anaesthetized rats. In some experiments the duodenal blood flow was estimated by laser-Doppler flowmetry. Exposure of the duodenum to acid (0.01 M HCl, 5 min) increased the alkaline secretion by approximately 85%. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1 intravenously or 0.3 mM intraluminally) blocked the secretory increment after mucosal acid exposure. Mean arterial pressure and basal alkaline secretion were markedly raised, whereas duodenal blood flow was decreased, when L-NAME was given intravenously (i.v.). Intraluminal (i.l.) administration left mean arterial pressure as well as duodenal blood flow unaltered, and the duodenal mucosal alkaline secretion was only slightly elevated. The stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) had no effect on either basal or acid-induced duodenal alkaline output. In animals receiving L-arginine (10 mg kg-1 min-1 i.v., or 3 mM i.l.) and L-NAME, the acid exposure elicited an increase in duodenal mucosal alkaline secretion, similar to that observed in controls. The results suggest that the acid-induced increase in duodenal mucosal alkaline secretion involves NO synthesis, which takes place close to the lumen, probably within the mucosa.