Mañana, JUEVES, 24 DE ABRIL, el sistema se apagará debido a tareas habituales de mantenimiento a partir de las 9 de la mañana. Lamentamos las molestias.
Biphasic effect of diabetes on neuronal nitric oxide release in rat mesenteric arteries
Entity
UAM. Departamento de Fisiología; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)Publisher
Public Library of ScienceDate
2016-06-07Citation
10.1371/journal.pone.0156793
PLos ONE 11.6 (2016): e0156793
ISSN
1932-6203DOI
10.1371/journal.pone.0156793Funded by
This study was supported by Ministerio de Economía y Competitividad (SAF2012-38530). ES received a FPI-UAM fellowship. FEX is recipient of research fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil)Project
Gobierno de España. SAF2012-38530Editor's Version
http://dx.doi.org/10.1371/journal.pone.0156793Subjects
Diabetes; Neuronal; Arteries; Vasoconstriction; MedicinaRights
© 2016 Sastre et al.Abstract
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
Files in this item
Google Scholar:Sastre, Esther
-
Caracuel, Laura
-
Blanco Rivero, Javier
-
Callejo, María
-
Xavier, Fabiano E.
-
Balfagón, Gloria
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