Peculiarities of the influence of antihypertensive therapy on endothelial function, oxidative stress and immune activation in obese patients

Abstract

This article aims to improve combined antihypertensive therapy on the basis of studying the antioxidant properties of bisoprolol and indapamid, their impact on endothelial dysfunction (ED) and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. A combination of a β-blocker (BAB) with a diuretic (D) (bisoprolol 2.5, 5, 10 mg and indapamid 1.5–2.5 mg/day) was prescribed to 102 patients with essential hypertension of 1–3 grades, 30 to 65 years old (mean age – 54.54 ± 0.91 years), who previously had not been receiving regular antihypertensive therapy. The daily dose of bisoprolol was administered by continuous slow titration, starting with low doses of 1.25 mg/day. Of the patients 82 were women and 20 men, the duration of disease averaged 9.0 ± 0.71 years. The control group included 16 healthy subjects matched for age and sex. The level of stable terminal metabolites of nitric oxide NO (nitrite NO2– and nitrate NO3–), the concentration of S-nitrosothiol and NO-synthases (NOS), SOD, and catalase activity was determined biochemically. The contents of serum 8-iso-PgF2α (8-isoprostane), TNF-alpha and its type I soluble receptor (sTNF-αRI) were determined in all subjects using the “8-isoprostane ELISA” (Usbiological,USA), “ProCon TNFα” (ProteinContour,Russian Federation) and “sTNF-RI EASIA” (BioSource Europe SA,Belgium) ELISA kits, respectively. During the course of combined antihypertensive therapy we observed a significant decrease of S-nitrosothiols levels, i-NOS activity, reduction of TNF-α type I of its soluble receptor (sTNF-αRI), and oxidative stress marker – 8-iso-PgF2α in the examined patients. Nitrites and nitrates serum levels, activity of e-NOS, superoxide dismutase and catalase, by contrast, were increased in patients with hypertension and concomitant obesity. These changes may reflect the fact that against the background of the therapy there was a reduction in tension of oxidative stress, which leads to an improvement in endothelial function. Significant reduction ratio of TNF-α/sTNF-αRI shows suppression of autoimmune and apoptotic activity in patients under treatment. Thus, the improvement of endothelial function, a significant decrease in autoimmune activation due to lower tension of oxidative stress in the examined patients optimizes use of a combination of bisoprolol and indapamid for differentiated therapy in hypertensive patients with obesity.