Local venomotor response to intravenous infusion of substance P and glyceryl trinitrate in systemic sclerosis.

Endothelial injury has been shown in ultrastructural studies in systemic sclerosis (SSc). In the present study, we tested the functional response of the endothelium in the early phase of the disease and at a more advanced stage. Substance P (SP) (25 and 50 ng) and glyceryl trinitrate (GT) (100 and 200 ng) were infused intravenously in 6 control subjects and in 6 female patients affected with early systemic sclerosis (SSc) to verify whether or not a lack of endothelial function could be detected. Venous compliance was assessed with a linear variable differential technique. Endothelial injury was evaluated by the von Willebrand Factor Antigen (vWF:Ag) plasma level and platelet aggregation by the platelet aggregate ratio (PAR). Endothelial-mediated response to SP was deficient in SSc patients in comparison with controls, whereas endothelium independent vasodilation was detected after the infusion of GT both in patients and controls. All vWF:Ag levels were in the normal range while in vivo platelet aggregation was increased as demonstrated by the PAR levels in the SSc subjects. The experiment was repeated in the same patients when the clinical status worsened and the levels of vWF:Ag were noted to rise: the endothelium dependent vasodilatory response to SP was still deficient as before and a decrease in vasodilatory response to GT was noted. vWF:Ag levels were significantly increased and the PAR still demonstrated an increased platelet aggregation. These data clearly indicate that an early functional deficit of the endothelial function is present before the onset of extensive visceral and skin involvement. The mechanism that provokes the impairment of the endothelial function need further investigation.