Plasma endothelin concentration was measured separately in each hand before and after unilateral whole-hand cooling in 23 patients (5 men, 18 women; mean age 35.2 [19-52] years) thought to have primary Raynaud's syndrome (Raynaud's disease). The diagnosis was confirmed, after excluding other causes, by strain-gauge plethysmography demonstrating cold-induced vasospasm in 8, disproved in 15. In the Raynaud patients (but not in the others) the plasma concentration of endothelin on the cooled side increased from 5.13 +/- 0.18 to 6.34 +/- 0.35 pg/ml (P < 0.05). On the non-cooled side there occurred a brief rise in endothelin concentration from 5.10 +/- 0.18 to 6.23 +/- 0.35 pg/ml (P < 0.05), although there had been no evidence of vasospasm. There had been no difference between the two sides in endothelin concentration before the cold provocation. The results suggest that cold provocation in primary Raynaud's syndrome causes an increase in endothelin liberation and that this plays a role in the pathogenesis of the vasospasms. Apparently not only local but also reflex mechanisms contribute to this.

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