Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction

Research output: Contribution to journalJournal articlepeer-review

Standard

Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction. / Klein, Anika ; Joseph, Philomeena D ; Christensen, Vibeke Grøsfjeld; Jensen, Lars Jørn; Jacobsen, Jens Christian Brings.

In: American Journal of Physiology: Heart and Circulatory Physiology, Vol. 315, No. 3, 2018, p. H644-H657.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Klein, A, Joseph, PD, Christensen, VG, Jensen, LJ & Jacobsen, JCB 2018, 'Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction', American Journal of Physiology: Heart and Circulatory Physiology, vol. 315, no. 3, pp. H644-H657. https://doi.org/10.1152/ajpheart.00111.2018

APA

Klein, A., Joseph, P. D., Christensen, V. G., Jensen, L. J., & Jacobsen, J. C. B. (2018). Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction. American Journal of Physiology: Heart and Circulatory Physiology, 315(3), H644-H657. https://doi.org/10.1152/ajpheart.00111.2018

Vancouver

Klein A, Joseph PD, Christensen VG, Jensen LJ, Jacobsen JCB. Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction. American Journal of Physiology: Heart and Circulatory Physiology. 2018;315(3):H644-H657. https://doi.org/10.1152/ajpheart.00111.2018

Author

Klein, Anika ; Joseph, Philomeena D ; Christensen, Vibeke Grøsfjeld ; Jensen, Lars Jørn ; Jacobsen, Jens Christian Brings. / Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction. In: American Journal of Physiology: Heart and Circulatory Physiology. 2018 ; Vol. 315, No. 3. pp. H644-H657.

Bibtex

@article{cc6e85c1c88c4ebfbbac92f4a135d353,
title = "Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction",
abstract = "Inward remodeling of resistance vessels is an independent risk factor for cardiovascular events. Thus far, the remodeling process remains incompletely elucidated, but the activation level of the vascular smooth muscle cell (VSMC) appears to play a central role. Accordingly, previous data suggest that an antagonistic and, supposedly beneficial, response - outward remodeling - may follow prolonged vasodilatation. This study aims to determine if 1) outward remodeling follows 3 days of vessel culture without tone, 2) a similar response can be elicited in a much shorter 4-hour time frame and finally 3) a 4-hour response can be prevented or reversed by the presence of vasoconstrictors in the medium. Cannulated mouse small mesenteric arteries (SMA) were organo-cultured for 3 days in the absence of tone, leading to outward remodeling that continued throughout the culture period. In more acute experiments in which cannulated SMAs were maintained in physiological saline without tone for 4 hours, we detected a similar outward remodeling that proceeded at a rate several times faster. In the 4-hour experimental setting, continuous vasoconstriction to approximately 50% tone by abluminal application of uridine 5{\textquoteright}-triphosphate (UTP) or norepinephrine (NE) + neuropeptide Y (NPY) prevented outward remodeling but did not cause inward remodeling. Computational modelling was used to simulate and interpret these findings and to derive time constants of the remodeling processes. It is suggested that depriving resistance arteries of activation will lead to eutrophic outward remodeling, which can be prevented by VSMC activation induced by prolonged vasoconstrictor exposure.NEW AND NOTEWORTHY: We have established an effective 4-hour method for studying outward remodeling in pressurized mouse resistance vessels ex vivo and have determined conditions that block the remodeling response. This allows for investigating the subtle but clinically highly relevant phenomenon of outward remodeling while avoiding both laborious 3-day organoid culture of cannulated vessels and in vivo experiments lasting several weeks.",
author = "Anika Klein and Joseph, {Philomeena D} and Christensen, {Vibeke Gr{\o}sfjeld} and Jensen, {Lars J{\o}rn} and Jacobsen, {Jens Christian Brings}",
note = "Online accepted manuscript",
year = "2018",
doi = "10.1152/ajpheart.00111.2018",
language = "English",
volume = "315",
pages = "H644--H657",
journal = "American Journal of Physiology: Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3",

}

RIS

TY - JOUR

T1 - Lack of Tone in Mouse Small Mesenteric Arteries Leads to Outward Remodeling, which can be Prevented by Prolonged Agonist-Induced Vasoconstriction

AU - Klein, Anika

AU - Joseph, Philomeena D

AU - Christensen, Vibeke Grøsfjeld

AU - Jensen, Lars Jørn

AU - Jacobsen, Jens Christian Brings

N1 - Online accepted manuscript

PY - 2018

Y1 - 2018

N2 - Inward remodeling of resistance vessels is an independent risk factor for cardiovascular events. Thus far, the remodeling process remains incompletely elucidated, but the activation level of the vascular smooth muscle cell (VSMC) appears to play a central role. Accordingly, previous data suggest that an antagonistic and, supposedly beneficial, response - outward remodeling - may follow prolonged vasodilatation. This study aims to determine if 1) outward remodeling follows 3 days of vessel culture without tone, 2) a similar response can be elicited in a much shorter 4-hour time frame and finally 3) a 4-hour response can be prevented or reversed by the presence of vasoconstrictors in the medium. Cannulated mouse small mesenteric arteries (SMA) were organo-cultured for 3 days in the absence of tone, leading to outward remodeling that continued throughout the culture period. In more acute experiments in which cannulated SMAs were maintained in physiological saline without tone for 4 hours, we detected a similar outward remodeling that proceeded at a rate several times faster. In the 4-hour experimental setting, continuous vasoconstriction to approximately 50% tone by abluminal application of uridine 5’-triphosphate (UTP) or norepinephrine (NE) + neuropeptide Y (NPY) prevented outward remodeling but did not cause inward remodeling. Computational modelling was used to simulate and interpret these findings and to derive time constants of the remodeling processes. It is suggested that depriving resistance arteries of activation will lead to eutrophic outward remodeling, which can be prevented by VSMC activation induced by prolonged vasoconstrictor exposure.NEW AND NOTEWORTHY: We have established an effective 4-hour method for studying outward remodeling in pressurized mouse resistance vessels ex vivo and have determined conditions that block the remodeling response. This allows for investigating the subtle but clinically highly relevant phenomenon of outward remodeling while avoiding both laborious 3-day organoid culture of cannulated vessels and in vivo experiments lasting several weeks.

AB - Inward remodeling of resistance vessels is an independent risk factor for cardiovascular events. Thus far, the remodeling process remains incompletely elucidated, but the activation level of the vascular smooth muscle cell (VSMC) appears to play a central role. Accordingly, previous data suggest that an antagonistic and, supposedly beneficial, response - outward remodeling - may follow prolonged vasodilatation. This study aims to determine if 1) outward remodeling follows 3 days of vessel culture without tone, 2) a similar response can be elicited in a much shorter 4-hour time frame and finally 3) a 4-hour response can be prevented or reversed by the presence of vasoconstrictors in the medium. Cannulated mouse small mesenteric arteries (SMA) were organo-cultured for 3 days in the absence of tone, leading to outward remodeling that continued throughout the culture period. In more acute experiments in which cannulated SMAs were maintained in physiological saline without tone for 4 hours, we detected a similar outward remodeling that proceeded at a rate several times faster. In the 4-hour experimental setting, continuous vasoconstriction to approximately 50% tone by abluminal application of uridine 5’-triphosphate (UTP) or norepinephrine (NE) + neuropeptide Y (NPY) prevented outward remodeling but did not cause inward remodeling. Computational modelling was used to simulate and interpret these findings and to derive time constants of the remodeling processes. It is suggested that depriving resistance arteries of activation will lead to eutrophic outward remodeling, which can be prevented by VSMC activation induced by prolonged vasoconstrictor exposure.NEW AND NOTEWORTHY: We have established an effective 4-hour method for studying outward remodeling in pressurized mouse resistance vessels ex vivo and have determined conditions that block the remodeling response. This allows for investigating the subtle but clinically highly relevant phenomenon of outward remodeling while avoiding both laborious 3-day organoid culture of cannulated vessels and in vivo experiments lasting several weeks.

U2 - 10.1152/ajpheart.00111.2018

DO - 10.1152/ajpheart.00111.2018

M3 - Journal article

C2 - 29775408

VL - 315

SP - H644-H657

JO - American Journal of Physiology: Heart and Circulatory Physiology

JF - American Journal of Physiology: Heart and Circulatory Physiology

SN - 0363-6135

IS - 3

ER -

ID: 196760459