Circulating endothelin-1 levels in patients with "a frigore" vascular acrosyndromes

The present study was designed to examine the role of endothelin-1 (ET-1), an endothelium-derived potent long-acting vasoconstrictor peptide, in vascular acrosyndromes with hypersensitivity to cold. Plasma ET-1 concentration was measured, before and after cold test, in 12 subjects with "a frigore" vascular acrosyndromes (9 females and 3 males, age range 17-59 years), of whom 6 were with primary Raynaud's phenomenon and 6 with essential acrocyanosis, and in 6 controls (5 females and 1 male, age range 21-37 years). Cold stimulation was performed by immersion of one hand into a water bath at 13 degrees C for 5 minutes. Blood samples were simultaneously drawn from an antecubital vein in the cooled side and in the contralateral arm at baseline, at the stop of cooling, at 10 and 90 minutes from the beginning of the cold challenge. Mean (+/-SD) baseline ET-1 plasma levels, as measured by radioimmunoassay, were higher in patients with "a frigore" vascular acrosyndromes (4.8 +/- 0.3 pmol/l) than in control subjects (1.9 +/- 0.1 pmol/l, p < 0.001). After hand cooling ET-1 rose in patients with "a frigore" vascular disorders to a peak value of 7.0 +/- 0.4 pmol/l, which was much greater than that observed in healthy subjects (2.7 +/- 0.4 pmol/l, p < 0.001). Absolute increase in ET-1 plasma concentrations from baseline to peak value was significantly higher in patients with "a frigore" vascular acrosyndromes than in normal subjects (2.2 +/- 0.3 vs 0.8 +/- 0.2 pmol/l, p < 0.001), being only in the former group the rise in ET-1 still detected 90 minutes after cold test. Plasma levels of ET-1 in the controlateral arm raised in a similar fashion, but absolute values were lower than in cooled arm. Circulating ET-1 levels in patients with primary Raynaud's phenomenon and essential acrocyanosis showed a similar pattern during the study. Our data demonstrate that in patients with "a frigore" vascular acrosyndromes baseline and cold-stimulated plasma ET-1 concentrations are increased. Further, in these vascular disorders, exaggerated ET-1 response to cold is prolonged. These findings suggest that increased ET-1 may contribute to an imbalance between vasoactive mediators in the cutaneous blood vessels contributing to the abnormal vasoconstriction to cold in these disorders. Alternatively, the increment in ET-1 release may represent a marker for endothelial cell damage in "a frigore" vascular acrosyndromes.