Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats.
PLoS One
; 11(1): e0146212, 2016.
Article
en En
| MEDLINE
| ID: mdl-26727368
ABSTRACT
BACKGROUND:
Autologous arteriovenous (AV) fistulas are the first choice for vascular access but have a high risk of non-maturation due to insufficient vessel adaptation, a process dependent on nitric oxide (NO)-signaling. Chronic kidney disease (CKD) is associated with oxidative stress that can disturb NO-signaling. Here, we evaluated the influence of CKD on AV fistula maturation and NO-signaling.METHODS:
CKD was established in rats by a 5/6th nephrectomy and after 6 weeks, an AV fistula was created between the carotid artery and jugular vein, which was followed up at 3 weeks with ultrasound and flow assessments. Vessel wall histology was assessed afterwards and vasoreactivity of carotid arteries was studied in a wire myograph. The soluble guanylate cyclase (sGC) activator BAY 60-2770 was administered daily to CKD animals for 3 weeks to enhance fistula maturation.RESULTS:
CKD animals showed lower flow rates, smaller fistula diameters and increased oxidative stress levels in the vessel wall. Endothelium-dependent relaxation was comparable but vasorelaxation after sodium nitroprusside was diminished in CKD vessels, indicating NO resistance of the NO-receptor sGC. This was confirmed by stimulation with BAY 60-2770 resulting in increased vasorelaxation in CKD vessels. Oral administration of BAY 60-2770 to CKD animals induced larger fistula diameters, however; flow was not significantly different from vehicle-treated CKD animals.CONCLUSIONS:
CKD induces oxidative stress resulting in NO resistance that can hamper AV fistula maturation. sGC activators like BAY 60-2770 could offer therapeutic potential to increase AV fistula maturation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Vasodilatadores
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Nitroprusiato
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Derivación Arteriovenosa Quirúrgica
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Donantes de Óxido Nítrico
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Insuficiencia Renal Crónica
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Óxido Nítrico
Límite:
Animals
Idioma:
En
Año:
2016
Tipo del documento:
Article