Biphasic effect of diabetes on neuronal nitric oxide release in rat mesenteric arteries
Introduction We analysed possible time-dependent changes in nitrergic perivascular innervation function from diabetic rats and mechanisms implicated. Materials and Methods In endothelium-denuded mesenteric arteries from control and four- (4W) and eight-week (8W) streptozotocin-induced diabetic rats...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/676613 |
| Acceso en línea: | http://hdl.handle.net/10486/676613 https://dx.doi.org/10.1371/journal.pone.0156793 |
| Access Level: | acceso abierto |
| Palabra clave: | Diabetes Neuronal Arteries Vasoconstriction Medicina |
| Sumario: | Introduction We analysed possible time-dependent changes in nitrergic perivascular innervation function from diabetic rats and mechanisms implicated. Materials and Methods In endothelium-denuded mesenteric arteries from control and four- (4W) and eight-week (8W) streptozotocin-induced diabetic rats the vasoconstriction to EFS (electrical field stimulation) was analysed before and after preincubation with L-NAME. Neuronal NO release was analysed in the absence and presence of L-arginine, tetrahydrobiopterine (BH4) and Larginine plus BH4. Superoxide anion (O2 -), peroxynitrite (ONOO-) and superoxide dismutase (SOD) activity were measured. Expressions of Cu-Zn SOD, nNOS, p-nNOS Ser1417, pnNOS Ser847, and Arginase (Arg) I and II were analysed. Results EFS response was enhanced at 4W, and to a lesser extent at 8W. L-NAME increased EFS response in control rats and at 8W, but not at 4W. NO release was decreased at 4W and restored at 8W. L-arginine or BH4 increased NO release at 4W, but not 8W. SOD activity and O2 - generation were increased at both 4W and 8W. ONOO- decreased at 4W while increased at 8W. Cu-Zn SOD, nNOS and p-NOS Ser1417 expressions remained unmodified at 4W and 8W, whereas p-nNOS Ser847 was increased at 4W. ArgI was overexpressed at 4W, remaining unmodified at 8W. ArgII expression was similar in all groups. Conclusions Our results show a time-dependent effect of diabetes on neuronal NO release. At 4W, diabetes induced increased O2 - generation, nNOS uncoupling and overexpression of ArgI and p-nNOS Ser847, resulting in decreased NO release. At 8W, NO release was restored, involving normalisation of ArgI and p-nNOS Ser847 expressions |
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