Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats

Irma L Geenen, Felix F Kolk, Daniel G Molin, Allard Wagenaar, Mathijs G Compeer, Jan H Tordoir, Geert W Schurink, Jo G De Mey, Mark J Post

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Resumé

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.

OriginalsprogEngelsk
Artikelnummere0146212
TidsskriftP L o S One
Vol/bind11
Udgave nummer1
Antal sider17
ISSN1932-6203
DOI
StatusUdgivet - 2016
Udgivet eksterntJa

Fingeraftryk

fistula
kidney diseases
nitric oxide
Rats
Nitric Oxide
rats
guanylate cyclase
Oxidative stress
Guanylate Cyclase
Animals
oxidative stress
vasodilation
carotid arteries
Vasodilation
animals
Histology
Jugular Veins
jugular vein
Nitroprusside
endothelium

Citer dette

Geenen, I. L., Kolk, F. F., Molin, D. G., Wagenaar, A., Compeer, M. G., Tordoir, J. H., ... Post, M. J. (2016). Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats. P L o S One, 11(1), [e0146212]. https://doi.org/10.1371/journal.pone.0146212
Geenen, Irma L ; Kolk, Felix F ; Molin, Daniel G ; Wagenaar, Allard ; Compeer, Mathijs G ; Tordoir, Jan H ; Schurink, Geert W ; De Mey, Jo G ; Post, Mark J. / Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats. I: P L o S One. 2016 ; Bind 11, Nr. 1.
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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.",
author = "Geenen, {Irma L} and Kolk, {Felix F} and Molin, {Daniel G} and Allard Wagenaar and Compeer, {Mathijs G} and Tordoir, {Jan H} and Schurink, {Geert W} and {De Mey}, {Jo G} and Post, {Mark J}",
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Geenen, IL, Kolk, FF, Molin, DG, Wagenaar, A, Compeer, MG, Tordoir, JH, Schurink, GW, De Mey, JG & Post, MJ 2016, 'Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats', P L o S One, bind 11, nr. 1, e0146212. https://doi.org/10.1371/journal.pone.0146212

Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats. / Geenen, Irma L; Kolk, Felix F; Molin, Daniel G; Wagenaar, Allard; Compeer, Mathijs G; Tordoir, Jan H; Schurink, Geert W; De Mey, Jo G; Post, Mark J.

I: P L o S One, Bind 11, Nr. 1, e0146212, 2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats

AU - Geenen, Irma L

AU - Kolk, Felix F

AU - Molin, Daniel G

AU - Wagenaar, Allard

AU - Compeer, Mathijs G

AU - Tordoir, Jan H

AU - Schurink, Geert W

AU - De Mey, Jo G

AU - Post, Mark J

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0146212

DO - 10.1371/journal.pone.0146212

M3 - Journal article

VL - 11

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 1

M1 - e0146212

ER -