Endothelial function of vascular segments that comprise a murine arteriovenous fistula

Approximately 60% of arteriovenous fistulas (AVFs) created in hemodialysis patients in the United States fail to mature. Understanding the underlying pathobiology is requisite to design and implement new treatments. Mechanisms responsible for AVF failure include intimal hyperplasia and poor lumen expansion. Compromised vasoreactivity also might play a role. Our murine AVF model comprises the external jugular vein (EJV) connected to the carotid artery (CA), establishing 3 component parts to the AVF, i.e., proximal CA, EJV, and distal CA. Upon AVF creation, the EJV is acutely exposed to higher pressures and disturbed flow, known causes of endothelial cell dysfunction. First, we tested the hypothesis that endothelial function is impaired in EJVs (193 ± 27 μm i.d.) from AVF mice (i.e., EJV-AVF; n= 5 males and 5 females) vs. EJVs (228 ± 18 μm i.d.) from naïve animals (EJV-Con; n=6 males and 4 females). Three days after creating the AVF, using isometric tension procedures, dose-dependent vasocontraction to the Thromboxane A2 (TxA2) receptor agonist U46619 was robust in the EJV-Con (p<0.05) but was absent in the EJV-AVF segment. Because vasocontraction is necessary to subsequently test endothelium-dependent vasorelaxation, our hypothesis could not be evaluated. Our second hypothesis was that endothelial function is impaired in the distal (185 ± 7 μm i.d.) vs. proximal (230 ± 10 μm i.d.) CA, secondary to disturbed flow patterns. U46619 -evoked vasocontraction was greater (p<0.05) in the proximal vs. distal CA segment of the AVF. Acetylcholine-evoked vasorelaxation was greater (p<0.05) in distal vs. proximal CA, whereas responses to sodium nitroprusside were similar between groups. These findings do not support our hypothesis and suggest that endothelial function is better in the distal vs. proximal CA of the AVF, whereas vascular smooth muscle function is similar between segments. Ongoing studies are evaluating endothelial function in each segment of the AVF 21-days after creation. Supported by R01HL153244 NIH/NIDDK (TL, YTS, JDS) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.