Calcitonin gene-related peptide, endothelin-1, the cutaneous microvasculature and Raynaud's phenomenon.

It has been argued that the digital cutaneous microvasculature is the site of the anomaly which causes Raynaud's phenomenon (RP). Both endothelin-1 (ET-1), a potent vasoconstrictor peptide present in the digital cutaneous microvasculature, and calcitonin gene-related peptide (CGRP), a powerful vasodilator present in digital cutaneous perivascular nerves, have been implicated in the pathogenesis of RP. Circulating ET-1 levels are raised, and there is a diminution of CGRP-containing perivascular nerves in finger skin in RP. We undertook a pharmacological study to investigate the sensitivity of the digital cutaneous microvasculature to intradermal ET-1 and CGRP. Differences were found in RP compared with normal digital skin, supporting the idea that the digital cutaneous microvasculature is actively involved in the pathogenesis of RP. In RP, the erythematous response to ET-1 was diminished at both 20 and 5 degrees C (a low temperature at which RP classically occurs) providing pharmacological support for the morphological evidence that in RP there is a deficiency of CGRP-containing nerves in the distal digital skin.