ORIGINAL RESEARCH article
Front. Physiol.
Sec. Vascular Physiology
This article is part of the Research TopicIntegrative Endothelial Signaling Mechanisms in Resistance ArteriesView all 3 articles
Vasomotor responses are similar between outbred UM-HET3 and inbred C57BL/6J male and female mouse mesenteric resistance arteries
Provisionally accepted
Robin Looft-Wilson*
Surya Naraynan
Kathleen SalmonEthan WunibaldBrian SimmonsConnor HaitzVishakha ShahMargaret Xu- College of William & Mary, Williamsburg, United States
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Objective: Genetically diverse UM-HET3 (HET3) mice have emerged as a more robust model of human large artery dysfunction than the commonly used inbred C57BL/6J (C57) mice. However, HET3 resistance artery function has not been examined. The purpose of this study was to examine HET3 versus C57 mesenteric resistance artery agonist-induced vasomotor responses to phenylephrine (PE) and acetylcholine (ACh), PE-induced myoendothelial feedback (endothelium-dependent feedback dilation to PE-induced vasoconstriction) and its underlying mechanisms, and expression of eNOS (an enzyme involved in endothelium-dependent dilation). Hypothesis: Vasomotor responses, mechanisms, and eNOS protein expression, will be similar between HET3 and C57 mesenteric resistance arteries of both sexes. Methods: 1st and 2nd order mesenteric arteries from male and female (8-18 wk old) HET3 and C57 mice were isolated and cannulated for pressure myography. Luminal diameter was measured (in a group-blinded manner) during cumulative addition of PE [10-9-10-5 M], then ACh [10-10-10-4 M]. In separate arteries, myoendothelial feedback was measured by diameter responses (constriction followed by endothelium-dependent feedback dilation) to 10-5 M PE over 20 min, +/- nitric oxide synthase (NOS) inhibition (10-5 M L-NAME) and +/- hyperpolarization inhibition with 35 mM KCl to assess myoendothelial feedback mechanisms. eNOS protein expression was measured by western blot. Results: Arteries from all groups were similar sizes (group mean range: 213-218 µm) and had negligible basal tone (group mean range: 1-4% constriction). PE-induced peak vasoconstriction (range: 71.0-73.8% constriction; n=11-12) and EC-50's (range: 1.03-1.54 µM) were similar between groups. ACh-induced peak vasodilation (range: 63.1-73.4% dilation) were also similar between groups. However, ACh EC-50 was significantly (p<0.05; ANOVA, Bon Ferroni) lesser in HET3-Female (0.047±0.021 µM) than C57-Female (4.22±1.97 µM) (p<0.05). Myoendothelial feedback responses were similar between groups (group mean range: 23.3-34.0% dilation) at 10 min, but significantly (p<0.01) greater in HET3-Male (56.5±4.9%) than C57-Male (38.8±2.2%) at 20 min (n=12-15), and were predominantly dependent on hyperpolarization mechanisms. eNOS/gapdh and eNOS/total protein expression were similar between the groups. Significance: This study reveals that HET3 mesenteric resistance arteries exhibit similar vasomotor responses to C57 arteries, with some indications of greater endothelium-dependent vasodilation in HET3, making it a viable mouse model for vascular studies.
Keywords: murine, Strain, Sex, Vasodilation, Vasoconstriction, myoendothelial, Phenylephrine, eNOS
Received: 26 Aug 2025; Accepted: 31 Oct 2025.
Copyright: © 2025 Looft-Wilson, Naraynan, Salmon, Wunibald, Simmons, Haitz, Shah and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Robin Looft-Wilson, rlooft@wm.edu
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