Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesity

IntroductionHypertension and impaired tissue perfusion are frequent comorbidities in obesity. Since resistance arteries are the primary regulators of peripheral resistance and hence, systemic blood pressure and local blood flow control, we hypothesized that resistance arteries isolated from obese mi...

Full description

Saved in:
Bibliographic Details
Main Authors: Darcy Lidington, Danny D. Dinh, Nan Chen, Hangjun Zhang, Yu-Qing Zhou, Scott P. Heximer, Daniel A. Winer, Alexandre Martchenko, Steffen-Sebastian Bolz
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2025.1602155/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849771808505462784
author Darcy Lidington
Darcy Lidington
Darcy Lidington
Danny D. Dinh
Danny D. Dinh
Danny D. Dinh
Nan Chen
Nan Chen
Hangjun Zhang
Hangjun Zhang
Yu-Qing Zhou
Scott P. Heximer
Scott P. Heximer
Daniel A. Winer
Daniel A. Winer
Daniel A. Winer
Daniel A. Winer
Alexandre Martchenko
Alexandre Martchenko
Alexandre Martchenko
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
author_facet Darcy Lidington
Darcy Lidington
Darcy Lidington
Danny D. Dinh
Danny D. Dinh
Danny D. Dinh
Nan Chen
Nan Chen
Hangjun Zhang
Hangjun Zhang
Yu-Qing Zhou
Scott P. Heximer
Scott P. Heximer
Daniel A. Winer
Daniel A. Winer
Daniel A. Winer
Daniel A. Winer
Alexandre Martchenko
Alexandre Martchenko
Alexandre Martchenko
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
author_sort Darcy Lidington
collection DOAJ
description IntroductionHypertension and impaired tissue perfusion are frequent comorbidities in obesity. Since resistance arteries are the primary regulators of peripheral resistance and hence, systemic blood pressure and local blood flow control, we hypothesized that resistance arteries isolated from obese mice would display augmented myogenic reactivity and altered vasomotor responses, compared to non-obese controls. MethodsEight-week-old C57BL/6J mice were fed either a high-fat diet (60% calories from fat; HFD) or a matched control diet for 16 weeks. Body weight, fasting blood glucose, oral glucose tolerance and insulin tolerance were measured. In parallel studies, we measured mean arterial pressure, conducted echocardiographic measurements of cardiac morphology and function and assessed skeletal muscle, mesenteric and cerebral resistance artery reactivity ex vivo with pressure myography. ResultsHFD mice exhibited substantial weight gain and metabolic dysfunction compared to controls. Left ventricular wall thickness and mass were increased in HFD mice, but no other morphological or functional cardiac parameters were different from controls. Blood pressure was modestly increased in HFD mice (from 81 to 87 mmHg; measured under anesthesia); however, contrary to our hypothesis, resistance arteries from HFD mice showed no overt microvascular phenotype in any microvascular bed tested (i.e., no differences in passive diameter, myogenic reactivity or vasomotor responses to phenylephrine or acetylcholine). ConclusionWe conclude that resistance artery function is unaltered in this diet-induced model of obesity with metabolic dysfunction.
format Article
id doaj-art-30e71feeaa094e66853b9b7f38b6a27b
institution DOAJ
issn 1664-042X
language English
publishDate 2025-08-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Physiology
spelling doaj-art-30e71feeaa094e66853b9b7f38b6a27b2025-08-20T03:02:30ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-08-011610.3389/fphys.2025.16021551602155Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesityDarcy Lidington0Darcy Lidington1Darcy Lidington2Danny D. Dinh3Danny D. Dinh4Danny D. Dinh5Nan Chen6Nan Chen7Hangjun Zhang8Hangjun Zhang9Yu-Qing Zhou10Scott P. Heximer11Scott P. Heximer12Daniel A. Winer13Daniel A. Winer14Daniel A. Winer15Daniel A. Winer16Alexandre Martchenko17Alexandre Martchenko18Alexandre Martchenko19Steffen-Sebastian Bolz20Steffen-Sebastian Bolz21Steffen-Sebastian Bolz22Steffen-Sebastian Bolz23Department of Physiology, University of Toronto, Toronto, ON, CanadaThe Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON, CanadaQanatpharma Ltd., Toronto, ON, CanadaDepartment of Physiology, University of Toronto, Toronto, ON, CanadaThe Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON, CanadaQanatpharma Ltd., Toronto, ON, CanadaDivision of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaDepartment of Physiology, University of Toronto, Toronto, ON, CanadaThe Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON, CanadaThe Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON, CanadaDepartment of Physiology, University of Toronto, Toronto, ON, CanadaThe Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON, CanadaDivision of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaBuck Institute for Research on Aging, Novato, CA, United StatesDepartment of Immunology, University of Toronto, Toronto, ON, CanadaDepartment of Physiology, University of Toronto, Toronto, ON, CanadaThe Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON, CanadaQanatpharma Ltd., Toronto, ON, CanadaDepartment of Physiology, University of Toronto, Toronto, ON, CanadaThe Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON, CanadaQanatpharma AG, Stans, SwitzerlandAphaia Pharma AG, Zug, SwitzerlandIntroductionHypertension and impaired tissue perfusion are frequent comorbidities in obesity. Since resistance arteries are the primary regulators of peripheral resistance and hence, systemic blood pressure and local blood flow control, we hypothesized that resistance arteries isolated from obese mice would display augmented myogenic reactivity and altered vasomotor responses, compared to non-obese controls. MethodsEight-week-old C57BL/6J mice were fed either a high-fat diet (60% calories from fat; HFD) or a matched control diet for 16 weeks. Body weight, fasting blood glucose, oral glucose tolerance and insulin tolerance were measured. In parallel studies, we measured mean arterial pressure, conducted echocardiographic measurements of cardiac morphology and function and assessed skeletal muscle, mesenteric and cerebral resistance artery reactivity ex vivo with pressure myography. ResultsHFD mice exhibited substantial weight gain and metabolic dysfunction compared to controls. Left ventricular wall thickness and mass were increased in HFD mice, but no other morphological or functional cardiac parameters were different from controls. Blood pressure was modestly increased in HFD mice (from 81 to 87 mmHg; measured under anesthesia); however, contrary to our hypothesis, resistance arteries from HFD mice showed no overt microvascular phenotype in any microvascular bed tested (i.e., no differences in passive diameter, myogenic reactivity or vasomotor responses to phenylephrine or acetylcholine). ConclusionWe conclude that resistance artery function is unaltered in this diet-induced model of obesity with metabolic dysfunction.https://www.frontiersin.org/articles/10.3389/fphys.2025.1602155/fullobesityinsulin resistancemyogenic activityresistance arteriesechocardiographyimpaired glucose tolerance (IGT)
spellingShingle Darcy Lidington
Darcy Lidington
Darcy Lidington
Danny D. Dinh
Danny D. Dinh
Danny D. Dinh
Nan Chen
Nan Chen
Hangjun Zhang
Hangjun Zhang
Yu-Qing Zhou
Scott P. Heximer
Scott P. Heximer
Daniel A. Winer
Daniel A. Winer
Daniel A. Winer
Daniel A. Winer
Alexandre Martchenko
Alexandre Martchenko
Alexandre Martchenko
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
Steffen-Sebastian Bolz
Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesity
Frontiers in Physiology
obesity
insulin resistance
myogenic activity
resistance arteries
echocardiography
impaired glucose tolerance (IGT)
title Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesity
title_full Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesity
title_fullStr Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesity
title_full_unstemmed Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesity
title_short Blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet-induced obesity
title_sort blood pressure is elevated in the absence of resistance artery dysfunction in a mouse model of diet induced obesity
topic obesity
insulin resistance
myogenic activity
resistance arteries
echocardiography
impaired glucose tolerance (IGT)
url https://www.frontiersin.org/articles/10.3389/fphys.2025.1602155/full
work_keys_str_mv AT darcylidington bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT darcylidington bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT darcylidington bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT dannyddinh bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT dannyddinh bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT dannyddinh bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT nanchen bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT nanchen bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT hangjunzhang bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT hangjunzhang bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT yuqingzhou bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT scottpheximer bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT scottpheximer bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT danielawiner bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT danielawiner bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT danielawiner bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT danielawiner bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT alexandremartchenko bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT alexandremartchenko bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT alexandremartchenko bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT steffensebastianbolz bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT steffensebastianbolz bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT steffensebastianbolz bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity
AT steffensebastianbolz bloodpressureiselevatedintheabsenceofresistancearterydysfunctioninamousemodelofdietinducedobesity