CALCITONIN-GENE-RELATED PEPTIDE, ENDOTHELIN-1, THE CUTANEOUS MICROVASCULATURE AND RAYNAUDS-PHENOMENON

It has been argued that: the digital cutaneous microvasculature is the site of the anomaly which causes Raynaud's phenomenon (RP), Both endo thelin-1 (ET-1), a potent vasoconstrictor peptide present in the digit al cutaneous microvasculature, and calcitonin gene-related peptide (CG RP), 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 per ivascular nerves in finger skin in RP. We undertook a pharmacological study to investigate the sensitivity of the digital cutaneous microvas culature to intradermal ET-1 and CGRP. Differences were found in RP co mpared 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 2 0 and 5 degrees C (a low temperature at which RP classically occurs) p roviding pharmacological support for the morphological evidence that i n RP there is a deficiency of CGRP-containing nerves in the distal dig ital skin.