[Endothelial immune activation and functional state in patients with hypertensive disease].

AIM: To investigate the nitric oxide (NO) system, the activity of endothelial NO synthase (e-NOS) and inducible NO synthase (i-NOS) in relation to the levels of tumor necrosis factor-α (TNF- α) and its soluble receptor type I (sTNFRI) depending on the grade of hypertensive disease (HD).

SUBJECTS AND METHODS: A total of 317 patients, including 284 patients aged 30 to 65 years (mean age 54.7±0.58 years) with Grades 1-3 HD who had not previously received regular antihypertensive therapy and 33 apparently healthy individuals, were examined at Kharkov City Clinical Hospital Eleven. Immune activation was judged by the serum levels of the proinflammatory cytokine TNF-α in all the examinees and y those of sTNFRI, which were measured by enzyme immunoassay. To study the endothelial functional state, the level of stable end metabolites of nitric oxide, that of S-nitrosothiol and the activity of NO synthases were biochemically determined in 100 patients from this group. A control group consisted of 16 apparently healthy individuals.

RESULTS: There were increases in the circulating levels of proinflammatory cytokines (TNF-α, sTNFRI), the content of S-nitrosothiol and the activity of i-NOS. At the same time, there were decreases in the activity of e-NOS and the level of end nitric oxide metabolites, such as nitrites and nitrates.

CONCLUSION: In patients with HD, the end metabolites of nitric oxide decrease, which indirectly shows a reduction in its vasoactive part, and the stable NO metabolite S-nitrosothiol increases. This is associated with enhanced NO oxidation under conditions of oxidative stress and endothelial dysfunction. The higher amount of S-nitrosothiol in the examinees may be associated with increased i-NOS. The immunoinflammatory activation mediated by the proinflammatory cytokines, particularly by the enhanced activity of TNF-α and sTNFRI, has been proven to play a role.