L’innervation sympathique artérielle (ISA) est un processus biologique complexe nécessitant un guidage fin des axones des neurones sympathiques par les artères. L’ISA est un élément clé de l’adaptation du système cardiovasculaire aux différentes contraintes (exposition au froid, exercice, etc.) : elle contrôle le diamètre des artères de résistance, donc le flux sanguin parvenant aux organes et la pression artérielle systémique via la modulation du tonus artériel. Son importance lors du vieillissement et dans de nombreux contextes pathologiques est de mieux en mieux reconnue et comprise. Son intégration à la prise en charge de nombreuses maladies (hypertension, cancer, etc.) permettrait d’en améliorer traitements et pronostic.

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 adaptive response of the cardiovascular system 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. Specific inactivation of EphA4 in sympathetic axons induced a loss of repulsion and increased sympathetic innervation of peripheral arteries throughout life. Functional consequences were a significant increase in arterial tone (resistivity and vasoconstriction), leading to an elevated systemic arterial blood pressure that reached to hypertension under stressful circumstances. These findings identify a novel pathway that negatively regulates sympathetic arterial innervation, and could participate to the appearance of idiopathic resistant hypertension.