Resistance arteries from UM-HET3 mice exhibit a robust myoendothelial feedback response

Objective: The genetically diverse UM-HET3 (HET3) mouse strain is a robust model for aging and a promising model for cardiovascular disease studies, however, resistance artery function has not been studied. The purpose of this study was to assess the mesenteric resistance artery myoendothelial feedback (MEF) response, an important intrinsic regulatory mechanism of vasomotor tone, of HET3 mice compared to the thoroughly studied C57BL/6J (C57) mice. MEF is the endothelial-dependent vasodilation that follows alpha-adrenergic-induced vasoconstriction, which is dependent on smooth muscle to endothelial gap junction communication. Hypothesis: MEF responses of HET3 arteries will not significantly differ from C57 arteries. Methods: MEF responses were measured in 1st and 2nd order mesenteric arteries (in a strain and sex-blinded manner), obtained from male and female HET3 and C57 mice (aged 8-17 wks), that were isolated and cannulated for pressure myography. Arteries were held at 37° C and at physiological pressure (75 mmHg) with no luminal flow, MOPS-buffered physiological salt solution (PSS) superfusion, and PSS + 1% BSA luminal perfusion. After 30-min equilibration to assess basal tone, luminal diameter was measured in response to addition of phenylephrine [10 -5 ] (PE) to the superfusate for 20 min, followed by addition of acetylcholine [10 -4 ] (ACh) to the superfusate for 15 min, then 10 min of flushing with Ca ++ -free PSS to determine maximal diameter. MEF responses are presented as % dilation at 20 min post PE addition, compared to peak constriction. Results: Basal tone, peak constriction to PE, peak dilation to ACh, and maximal diameter were not different between groups. After 20 minutes of PE superfusion, MEF responses (mean ± SEM) were 58.8 ± 4.7% in HET3 male (n=11), 43.5 ± 2.6% in HET3 female (n=12), 38.8 ± 2.2% in C57 male (n=15), and 47.8 ± 3.9% in C57 female (n=15) arteries. 1-way ANOVA (with Bonferroni post-hoc test) revealed that HET3 male arteries had significantly greater MEF responses than HET3 female (p<0.05) and C57 male (p<0.01), but not C57 female arteries. Conclusion: This study reveals that HET3 mice exhibit a strong MEF response and are a valid model for future resistance artery studies. Funded by NIH-1R15HL150570-01A1 (R.L-W.), the William & Mary Charles Center Undergraduate Summer Research Grant (E.W., K.S.), and the William & Mary FUSE program (C.H.). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.