Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis - Findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1

Objective. To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate wheth er production of endothelial-derived nitric oxide (NO) is disturbed in this disease. Methods. We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how t hese variables were related to one another, Plasma nitrate and 24-hour-urin ary excretion of nitrate in patients and controls were measured after a 72- hour nitrate-free-diet, using a gas chromatography/mass spectrometric metho d. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines w ere measured by enzyme-linked immunosorbent assay. The expression of E-sele ctin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. Results. Plasma nitrate and 24-hour-urinary-excretion of cGMP were signific antly elevated in patients compared with controls, while 24-hour-urinary-ex cretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1 , sVCAM-1, and sE-selectin were significantly elevated in the patients. Lev els of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a signifi cant correlation with sICAM-1 (P = 0.055), suggesting that activated endoth elial cells may produce plasma nitrate. Conclusion. NO synthesis is elevated in SSc patients, and the activated end othelial cell is a likely site of its production.