Work

EphrinA4/EphA4 controls blood pressure via arterial sympathetic innervation in male mice

Year: 2026

Type: article

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 EphA4flox-THCRE 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. The sympathetic nervous system regulates blood pressure, but how arterial sympathetic innervation is established remains unclear. Here, the authors show that EphrinA4/EphA4 signalling limits sympathetic arterial innervation, thereby controlling vascular resistance and systemic blood pressure.

Source: Nature Communications

DOI: 10.1038/s41467-026-78388-x