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 microenvironment and both of them release factors that contribute to find a balance between vasolidation and vasoconstriction. 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 vasolidation. Estrogen administration improved endothelial dysfunction in secondary RP. Neuropeptides and estrogens thus share the endothelial-dependent pathway, usually mediated by nitric oxide, in inducing vasolidation. 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.