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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.

The aim of this study was to investigate in human skin in vivo the role of nitric oxide in maintaining resting vascular tone, in the vasodilatation caused by local warming and by ultraviolet B light exposure, and in the response to exogenous calcitonin gene-related peptide (CGRP). Cutaneous blood flow was assessed by planimetry of the visible erythema or pallor and by laser Doppler flowmetry. Intradermal injection of the inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol), into forearm skin produced a visible pallor and a reduction of blood flow at a controlled ambient temperature of 21 degrees C. The control, NG-nitro-D-arginine methyl ester (D-NAME; 25 nmol) or NG-monomethyl-L-arginine (L-NMMA; 25 nmol) did not cause pallor or reduce blood flow. L-NAME and L-NMMA caused dose- and time-dependent increases in pallor, and reductions in cutaneous blood flow in skin that had been locally warmed by immersion in water at 45 degrees C and in skin that had been exposed to ultraviolet B light. D-NAME and D-NMMA at comparable concentrations did not have the effects on skin blood flow observed with the L forms. L-NAME and L-NMMA both inhibited the increased blood flow in human skin caused by the intradermal injection of CGRP (12.5 or 25 pmol). The reduction of CGRP-induced increase of blood flow by L-NAME was reversed by L-arginine. Neither D-NAME nor D-NMMA inhibited the increase in blood flow caused by CGRP. Neither L-NAME nor L-NMMA inhibited the increase in blood flow in human skin caused by the intradermal injection of prostaglandin E2 (63 pmol). The data show that nitric oxide is involved in the maintenance of resting blood flow in human skin and also in the cutaneous vasodilator responses to local warming, ultraviolet B irradiation, or injection of CGRP.

Vibration white finger or hand-arm vibration syndrome is the episodic blanching of the fingers in response to cold occurring in those who work with hand held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent paraesthesiae and pain are common in the hands and arms and these occur independently from the 'white attacks'. Symptoms can become severe enough to warrant a change of occupation. Industrial compensation may be awarded for vibration white finger but, at present, no simple or reliable objective diagnostic test is available. Calcitonin gene-related peptide (CGRP) is a neuropeptide with powerful vasodilator properties. A deficiency of immunoreactive CGRP nerve fibres has been previously demonstrated in the digital cutaneous microvasculature of patients with primary and secondary Raynaud's phenomenon with the distribution and quantity of other types of nerve fibres not being significantly altered. To determine if the innervation of the cutaneous microvasculature in vibration white finger was also abnormal skin biopsy samples from the fingers of 15 patients with vibration white finger, six healthy age matched controls who worked with vibrating machinery and 26 healthy age matched controls who were heavy manual workers without exposure to vibrating machinery were examined by immunohistochemistry. To try to correlate any histological abnormalities with clinical neurological deficit sensory nerve conduction studies have so far been performed in six patients with vibration white finger.(ABSTRACT TRUNCATED AT 250 WORDS)