Microvascular dysfunction and increased oxidative stress are major hallmarks of the
systemic sclerosis disease process. The primary objective of this study was to test whether there is a link between peak postocclusive
hyperemia and urinary levels of the
F2-isoprostane 15-F2t-IsoP (8-iso-PGF2alpha) in patients suffering from
systemic sclerosis. We enrolled 43 patients suffering from
systemic sclerosis, 33 patients with primary Raynaud's phenomenon (RP), and 25 healthy volunteers. Microvascular function was assessed using the postocclusive
hyperemia monitored by
laser Doppler flowmetry. Endothelium-independent response was monitored after 0.4 mg sublingual
nitroglycerin. Oxidative stress status was assessed by urinary levels of the
F2-isoprostane 15-F2t-IsoP using GC-MS. The peak postocclusive vascular conductance was altered in subjects with
systemic sclerosis and primary RP compared to controls (respectively 28 (7-48), 30 (13-48), and 39.9 (13-63) mV/mm Hg, p = 0.01).
F2-isoprostanes were increased in the
systemic sclerosis group compared to primary Raynaud's phenomenon and healthy controls (respectively 230 (155-387), 182 (101-284), and 207 (109-291) pg/mg, p = 0.006). In patients suffering from
systemic sclerosis, there was a significant inverse correlation between
F2-isoprostanes and postocclusive
hyperemia, expressed as raw data (R = -0.45, p = 0.007) or as an increase over baseline (R = -0.28, p = 0.04). Conversely, no correlation was found with the
nitroglycerin response. In conclusion, we provide evidence that there is an inverse correlation between postocclusive
hyperemia and urinary
F2-isoprostane levels in patients suffering from
systemic sclerosis. Whether
oxygen free radicals initiate the vascular dysfunction or whether there is an initial trigger that initiates both processes will need to be further clarified in future studies.