RESUMEN
We found activation c-fos protein in the NO synthase-containing neurons within the islands of Calleja (96.46 +/- 16.03 fos-immunoreactive nuclei per 50 mm section) in control and suppression of this activation after unilateral 6-hydroxydopamine lesions of dopaminergic mesostriatal system of brain (14.31 +/- 4.59 nuclei per section). Since the neuronal activity in the islands of Calleja is associated with the blood supply changes in the basal ganglia we propose that the suppression of c-fos protein expression in this structure after lesions of dopaminergic mesostriatal system reflects the disorders its blood supply.
Asunto(s)
Regulación de la Expresión Génica/fisiología , Neostriado/metabolismo , Vías Olfatorias/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Receptores Dopaminérgicos/metabolismo , Animales , Depresión Química , Regulación de la Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Masculino , Neostriado/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neurotoxinas/farmacología , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/metabolismo , Nitroglicerina/farmacología , Vías Olfatorias/efectos de los fármacos , Oxidopamina/farmacología , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacos , Ratas , Ratas Wistar , Receptores Dopaminérgicos/efectos de los fármacosRESUMEN
This study investigated the influence of the chronic cerebral dopamine deficiency after 6-hydroxydopamine lesions of dopaminergic mesostriatal system and NO pathways on the length-tension relation in vascular smooth muscles to their distension. Experiments were performed on isolated strips of rat portal vein. The results indicate that the attenuated contraction responses and the increased stiffness of vascular smooth muscles to the distension in a chronic mesostriatal dopamine deficiency. It was found that these responses may be, in part, normalized after a long-term L-arginine administration. The same changes were marked in the responses of intact vascular strips after the inhibition of NO-synthase activity and L-arginine perfusion. It has been suggested that, in a chronic mesostriatal dopamine deficiency, the reduced vascular reactivity was due to the decreasing of NO synthesis by endothelium and L-arginine could be used in the treatment of these vascular disorders.
Asunto(s)
Cuerpo Estriado/fisiología , Dopamina/deficiencia , Contracción Muscular/fisiología , Músculo Liso Vascular/fisiología , Óxido Nítrico/fisiología , Adrenérgicos , Animales , Arginina/farmacología , Cuerpo Estriado/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Oxidopamina , Vena Porta/efectos de los fármacos , Vena Porta/fisiología , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Experiments were performed on vessels of the femoral vascular bed of anesthetized dogs and on isolated rings of the rat pulmonary artery, vena cava, and thoracic aorta. Vintoperol was administered intra-arterially (0.01, 0.1, and 0.3 mg/kg/min for 10 min) or added in vitro (10(-4) M). De-endothelialization by saponin (0.5 mg/ml for 5 min) of intact vascular beds or mechanical endothelium removal in rings decreased vasodilation or relaxation by 50-60% vs. control. In de-endothelialized vascular beds, vintoperol (0.3 mg/kg/min) increased blood flow by 18 +/- 5% but 47 +/- 4% under control conditions (p < 0.05). Methylene blue (10 mg/kg) reduced the increment of blood flow to vintoperol from 47 +/- 4 to 24 +/- 4% (p < 0.05). After de-endothelialization of the isolated pulmonary artery, relaxation of precontracted segments was reduced (21 +/- 4% vs. 56 +/- 5% under control conditions; p < 0.05). Vintoperol-induced relaxation of vascular rings was also inhibited by gossypol (2 x 10(-5) M) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) depended on the duration of exposure to the inhibitors. In conclusion, relaxation to vintoperol must be mediated by the release of endothelium-derived nitric oxide.