Fig. 2

Potential actions of VNS on different pathogenetic mechanisms involved in PAH. Pulmonary arterial vasoconstriction, right ventricular (RV) dysfunction and systemic inflammation are core mechanisms in the pathogenesis of PAH. They may be related to autonomic imbalance that is common in PAH, with an increased sympathetic and decreased parasympathetic tone. Vasoconstriction, RV dysfunction and inflammation lead to remodeling in the RV and pulmonary vessels, which eventually exacerbate the pathophysiology of PAH. In principle, VNS could target therapeutically these mechanisms in the following ways: VNS produces NO-mediated vasodilation in the pulmonary circulation via vagal bronchopulmonary branches. VNS renormalizes RV function via efferent and possibly afferent cardiac vagal fibers. VNS down-modulates cytokine-mediated immune response via branches that terminate in the spleen. VNS chronically restores autonomic imbalance, possibly via re-setting vagal and non-vagal autonomic reflexes between the brain and periphery