Heterogeneous Effects of Aging on Vasomotor Function in Large and Small Arteries
Authors: Kim Hyoseon , Luttrell Meredith , Shin Song Yi , Holly Dylan , Dezell Hannah , Woodman Christopher , Massett Michael 
Published: June 2021

Aging is associated with impaired vasomotor function. However, due to structural and functional differences between conduit and elastic arteries, the effect of aging on vasomotor function might vary throughout the vascular tree. Thus, the purpose of this study was to determine if there are any aging‐related differences in endothelial function between different sized vessels throughout the vascular tree. Large (abdominal aorta (AA), iliac artery (IA)) and small (femoral artery (FA), gastrocnemius feed artery (GFA)) arteries were isolated from young (4 months) and old (24 months) male Fischer 344 rats. Vessels were cut into 2 mm segments and mounted in a wire myograph. Cumulative concentrations of phenylephrine (PE, 1 × 10−9 M – 1 × 10−5 M) were used to assess contractile responses. To assess relaxation responses, vessels were treated with increasing concentrations of the endothelium‐dependent vasodilator acetylcholine (ACh) and the endothelium‐independent vasodilator sodium nitroprusside (SNP) (1 × 10−9 M – 1 × 10−5 M). Contractile responses to PE were significantly greater in all vessels from young rats compared with old rats. Aging‐related differences in the relaxation responses to ACh varied among the vessels. Relaxation responses to ACh were significantly impaired in AA from old rats compared to young rats (P = 0.0008). ACh‐induced relaxation in IA tended to be reduced in vessels from old rats compared with young (P = 0.051). In contrast, there were no differences for responses in FA (P = 0.10) and GFA (P = 0.80). For the endothelium independent dilator SNP, only AA showed significant differences in relaxation responses between arteries from young and old rats. Relaxation responses to low concentrations of SNP (10−9 M – 10−7 M) were blunted in AA from old rats, but maximal relaxation was not different between young and old. To investigate a potential mechanism for reduced endothelium dependent relaxation in AA and IA, protein content of eNOS, caveolin‐1 (CaV‐1), calmodulin (CaM) and their interactions (CaV‐1:eNOS and CaM:eNOS) were assessed by immunoblot analysis. CaV‐1 is a negative regulator of eNOS activity, whereas CaM is a positive regulator. In AA, both CaV‐1:eNOS and CaM:eNOS were reduced in vessels from old rats compared with young rats. CaV‐1:eNOS was increased in IA from old rats compared with young rats. Collectively, these results indicate that age‐related impaired responses to ACh occur in large but not smaller arteries. The impaired responses were associated with changes in protein levels of CaV‐1 and CaM. These results suggest that non‐uniform changes in protein:protein interactions might contribute to heterogeneous changes in endothelial function with aging.Support or Funding InformationThe authors recognize the support of the National Institute on Aging for providing the animals used in this study. This work was supported by AHA (4150031) and Sydney and J.L Huffines Institute for Sports Medicine and Human Performance Grants to CW, and Texas A&M College of Education Strategic Research Award to SS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.