Estrogens and Neuropeptides in Raynaud's phenomenon

Raynaud's phenomenon (RP) is characterized by ischemia and reperfusion of the extremities. Vasomotor instability is due to a microcirculatory disturbance that may be linked to different events involving the endothelium or peripheral nerve terminals. Endothelium and nerve endings sense the modifications of the micro-environment and both of them release factors that contribute to find a balance between vasodilation and vasoconctriction. Moreover, estrogens may contribute to control vascular tone regulating finger skin circulation. A loss of neuropeptides has been shown in secondary RP where supplementation with factors derived from nerve endings has been demonstrated to induce a potent vasodilation. Estrogen administration improved endothelial dysfunction in secondary RP. Neuropeptides and estrogens thus share the endothelial-dependent pathway, usually mediated by nitric oxide, in inducing vasodilation. The network directed by the endothelium is in reality controlled by a neuro-hormonal axis composed by neuropeptides and estrogens. This delicate balance keeps the vascular tone, and its dysfunction may lead to a dysregulation of vascular tone, manifest in clinics as a primary or secondary RP.