Abstract: TH-PO747
Reduced Endothelium-Dependent Vasodilation and Impaired Arteriovenous Fistula (AVF) Development in a Rat Model with CKD
Session Information
- Hemodialysis: Vascular Access - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Dialysis
- 603 Hemodialysis: Vascular Access
Authors
- Shiu, Yan-Ting, University of Utah, SALT LAKE CITY, Utah, United States
- He, Yuxia, University of Utah, SALT LAKE CITY, Utah, United States
- Machin, Daniel R, University of Utah, SALT LAKE CITY, Utah, United States
- Tey, CS Jason, University of Utah, SALT LAKE CITY, Utah, United States
- Fan, Jack Z, University of Utah, SALT LAKE CITY, Utah, United States
- Chen, Zhen, Beckman Research institute, City of Hope, Duarte, California, United States
- Leary, Miriam Elizabeth, University of Texas at Austin, Austin, Texas, United States
- Tanaka, Hirofumi, University of Texas at Austin, Austin, Texas, United States
- Donato, Tony J, University of Utah, SALT LAKE CITY, Utah, United States
- Cheung, Alfred K., University of Utah, SALT LAKE CITY, Utah, United States
Background
AVF maturation failure results from neointimal hyperplasia (NH) and insufficient dilation of lumen, but the latter remains largely unexplored. We investigated endothelium-dependent vasodilation (EDV) and AVF development in a clinically relevant CKD-AVF model.
Methods
CKD was induced in 10-week-old Wistar male rats fed a 0.25% adenine-containing diet (AD) for 10 wk. EDV of femoral arteries was non-invasively assessed at baseline, 10 wk on AD, and 4 wk after returning to normal diet (ND). Gene expression of key endothelial regulators, including transcription factors Krüppel-like factor 2 (KLF2) and KLF4 and their target endothelial nitric oxide synthase (eNOS), was assessed in the aorta of CKD and normal rats. Femoral AVFs were created in CKD and normal rats. AVF lumen diameter was measured by ultrasound, and animals were euthanized for histology.
Results
In CKD rats, plasma creatinine and BUN increased 3-fold after 10 wk on AD, and the elevated levels persisted after return to ND for 4 wk. EDV was lower after AD (5.6±2.2%) than baseline (16.3±1.7%)(p<0.05; n=8) and remained impaired after CKD rats returned to ND (6.0±2.8%, n=4). Aortic eNOS expression was lower in CKD rats than in control rats (0.77±0.25 vs. 2.84±0.71; p<0.05; n=4 each), and the expression of KLF2/4 was also lower in CKD. At 4 wk after AVF creation, while NH was observed in both groups, AVF lumen was significantly smaller in CKD than in control rats (Fig. 1).
Conclusion
CKD decreased the expression of KLF2/4 and eNOS, which may decrease the NO availability and NO-mediated dilation. CKD may impair AVF dilation via decreased EDV.
Funding
- NIDDK Support