Serum endothelin-1 concentrations and cold provocation in primary Raynaud's phenomenon

To determine whether the vasoconstriction in Raynaud's phenomenon is associated with raised concentrations of the endothelium-derived vasoconstrictor endothelin (ET-1), responses to cold pressor testing were examined in 7 subjects with primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1 levels (pg/ml), as measured by radioimmunoassay, were three times higher in Raynaud's subjects (5·3 [SEM 1·7] pg/ml) than in controls (1·7 [0·3]). With progressive local cooling digital arterial pulsatility, as measured by plethysmography, fell earlier and to a greater extent in Raynaud's subjects than in controls, with a half-maximum decrement in pulsatility occurring at 27 [2·6]°C and 18 [0·5]°C, respectively. Temperature reduction sufficient to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1 concentrations in both groups that were greater in Raynaud's (10·3 [4·4] pg/ml) than in control subjects (2·7 [0·9] pg/ml). Serum ET-1 in the contralateral arm rose in parallel to but to a lesser extent than that in the cold-challenged arm. Increases in ET-1 concentrations were temporally related to loss of pulsatility but followed the onset of symptoms. Thus the increased basal and stimulated serum endothelin concentrations in Raynaud's disease are associated with the enhanced, prolonged vasospasm of this disorder.