EphrinA4/EphA4 controls blood pressure via arterial sympathetic innervation in male mice
Abstract
The autonomic sympathetic nervous system innervates peripheral resistance arteries, thereby controlling arterial diameter and modulating blood supply to organs and arterial tone. Despite its fundamental role in blood flow regulation and cardiovascular adaptation to challenging situations, how sympathetic arterial innervation develops remains poorly understood. We here show that sympathetic arterial innervation is regulated by the axonal guidance molecule EphrinA4 in arterial Smooth Muscle Cells (SMCs), which repels sympathetic axons via the EphA4 receptor. Using the EphA4 flox -TH CRE mouse, we specifically inactivated EphA4 in sympathetic axons, inducing a loss of repulsion and increased sympathetic innervation of peripheral arteries throughout life. Functional consequences included a significant increase in arterial tone, including resistivity and vasoconstriction, associated with elevated systemic arterial blood pressure at rest and a marked increase during acute stress. These findings identify a pathway that negatively regulates sympathetic arterial innervation and could contribute to elevated systemic blood pressure in male mice.
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BibTeX
@article{simonnet2026ephrina4epha4,
title = {{EphrinA4/EphA4 controls blood pressure via arterial sympathetic innervation in male mice}},
author = {Emilie Simonnet and Sabrina Martin and José Vilar and Virginie Monceau and Emilie Vessieres and Gaëtan Pallot and Marc Rio and Sonia Taib and Jean-Claude do Rego and Jean-Luc do Rego and Colin Salaün and Fabrice Raynaud and Luc Pardanaud and Dominique Laude and Nadine Bouby and Anne-Clémence Vion and Anne Eichmann and Jean-Sébastien Silvestre and Daniel Henrion and Isabelle Brunet},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78388-x},
url = {https://www.nature.com/articles/s41467-026-78388-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - EphrinA4/EphA4 controls blood pressure via arterial sympathetic innervation in male mice
AU - Emilie Simonnet
AU - Sabrina Martin
AU - José Vilar
AU - Virginie Monceau
AU - Emilie Vessieres
AU - Gaëtan Pallot
AU - Marc Rio
AU - Sonia Taib
AU - Jean-Claude do Rego
AU - Jean-Luc do Rego
AU - Colin Salaün
AU - Fabrice Raynaud
AU - Luc Pardanaud
AU - Dominique Laude
AU - Nadine Bouby
AU - Anne-Clémence Vion
AU - Anne Eichmann
AU - Jean-Sébastien Silvestre
AU - Daniel Henrion
AU - Isabelle Brunet
PY - 2026
DA - 2026/10/14
JO - Nature Communications
DO - 10.1038/s41467-026-78388-x
UR - https://www.nature.com/articles/s41467-026-78388-x
AB - The autonomic sympathetic nervous system innervates peripheral resistance arteries, thereby controlling arterial diameter and modulating blood supply to organs and arterial tone. Despite its fundamental role in blood flow regulation and cardiovascular adaptation to challenging situations, how sympathetic arterial innervation develops remains poorly understood. We here show that sympathetic arterial innervation is regulated by the axonal guidance molecule EphrinA4 in arterial Smooth Muscle Cells (SMCs), which repels sympathetic axons via the EphA4 receptor. Using the EphA4 flox -TH CRE mouse, we specifically inactivated EphA4 in sympathetic axons, inducing a loss of repulsion and increased sympathetic innervation of peripheral arteries throughout life. Functional consequences included a significant increase in arterial tone, including resistivity and vasoconstriction, associated with elevated systemic arterial blood pressure at rest and a marked increase during acute stress. These findings identify a pathway that negatively regulates sympathetic arterial innervation and could contribute to elevated systemic blood pressure in male mice.
SN - 2041-1723
ER -