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.References
Alisson, D. B., Gallagher, D., & Heo, M. (1997). Body mass index and all-cause mortality among people age 70 and over the longitudinal study of aging. International Journal of Obesity, 21, 424–431.
Allison, S. J. (2016). Oxidative stress and immune activation in hypertension. Nature Reviews Nephrology, 12, 4.
Ambrosova, T. N., Kovaljova, O. N., & Ashcheulova, T. V. (2009). Vzaimosvjaz’ aktivnosti FNO-α s razvitiem insulinorezistentnosti u bol’nyh s arterial’noj gipertenziej, associirovannoj s ozhireniem [Interrelation of activity ФНО-α with development of an insulinorezistentnost in patients with the arterial hypertension associated with obesity]. Lіki Ukrajiny, 127, 120–123 (in Russian).
Arroyo-Espliguero, R., Avanzas, P., Quiles, J., & Kaski, J. (2009). C-reactive protein predicts functional status and correlates with left ventricular ejection fraction in patients with chronic stable angina. Atherosclerosis, 205(1), 319–324.
Ashcheulova, T. V., Zaika, M. V., & Gerasimchuk, N. N. (2007). Vzaimosvjaz’ immunnoj aktivacii i oksidativnogo stressa pri progressirovanii arterial’noj gipertenzii [Relationships between immune activation and oxidative stress in arterial hypertension progression]. Ukrainskij Terapevticheskij Zhurnal, 2, 12–15 (in Russian).
Azra, M., & Feely, J. (2005). Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension, 46, 1118–1122.
Bautista, L. E., Veram, L. M., & Arenas, I. A. (2005). Independent association bet-ween inflammatory markers (C-reactive protein, interleukin 6 and TNF-alpha) and essential hypertension. Journal of Human Hypertension, 19, 149–154.
Buemui, M., Corica, F., & Marino, D. (2000). Cardiovascnlar remodeling, apoptosis and drugs. American Journal of Hypertension, 13, 450–454.
Chaudhary, M., & Chaudhary, S. (2017). Unravelling the lesser known facets of angiotensin II type 1 receptor. Current Hypertension Reports, 19, 1.
Chow, B. S. M., & Allen, T. J. (2016). Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease. Clinical Science, 130(15), 1307–1326.
Dyer, A. R., Elliott, P., & Shipley, M. (1994). Body mass index and association of sodium and potassium with blood pressure in intersalt. Hypertension, 23, 729–736.
Gerasimchuk, N. N. (2008). Vazoaktivnyj pul oksida azota u bol’nyh s arterial’noj gipertenziej i izbytochnoj massoj tela [Vasoactive nitric oxide pool at overweight patient with arterial hypertension]. Circulation and Haemostasis, 3, 21–26 (in Russian).
Knjaz’kova, I. I. (2013). Terapevticheskaja jeffektivnost’ bisoprolola u bol’nyh so stabil’noj stenokardiej. Zdorov’ja Ukrajiny, 17, 13–15 (in Russian).
Kovaljova, O. N., Ashcheulova, T. V. (2002). Faktor nekroza opuholej-α. Klinicheskoe issledovanie aktivnosti pri arterial’noj gipertenzii [Tumor necrosis factor-α. Clinical trial of activity at arterial hypertension]. Іmunologіja ta Alergologіja, 4, 64–66 (in Russian).
Kovaljova, O. N., Ashcheulova, T. V., & Gerasimchuk, N. N. (2015). Vzaimo-svjaz’ immunnoj aktivacii i oksidativnogo stressa u bol’nyh gipertonicheskoj bolezn’ju i ih korrekcija kombinirovannoj antigipertenzivnoj terapiej [Relati-onship of immune activation and oxidative stress in patients with hypertension and their correction combined antihypertensive therapy]. Nauchnye Vedomosti Belgorodskogo Gosudarstvennogo Universiteta Medicina Far-macija, 213, 52–59 (in Russian).
Kovaljova, O. N., Ashcheulova, T. V., Gerasimchuk, N. N., & Safargalina-Kornilo-va, N. A. (2015). Rol’ oksidativnogo stressa v stanovlenii i progressirovanii gipertonicheskoj bolezni [Role of oxidative stress in the formation and progression of hypertensive disease]. Nauchnye Vedomosti Belgorodskogo Gosudarstvennogo Universiteta Medicina Farmacija, 201, 5–10 (in Russian).
Kovaljova, O. N., Belovol, A. N., & Zaika, M. V. (2005). Rol’ oksidativnogo stressa v kardiovaskuljarnoj patologii [Role of an oxidative stress in cardiovascular pathology]. AMN Ukrajiny, 11(4), 660–670 (in Russian).
Kovaljova, O. N., Shapovalova, S. A., & Gerasimchuk, N. N. (2005). Kombiniro-vannaja terapija arterial’noj gipertenzii [Combination therapy of hypertension]. Plejada, Harkiv (in Russian).
Lahera, V., Cachofeiro, V., & Heras, N. (2011). Interplay of hypertension, inflammation, and angiotensin II. American Journal of Hypertension, 24, 1059–1059.
Li, H., Zhu, X., Wang, A., & Wang, G. (2012). Co effect of insulin resistance and biomarkers of inflammation and endothelial dysfunction on hypertension. Hypertension Research, 35(5), 513–517.
London, G. M. (2004). Efficacy of indapamide 1.5 mg, sustained release, in the lowering of systolic blood pressure. Journal of Human Hypertension, 18, 9–14.
Neutel, J., 2011. Combination therapy in hypertension. Springer Healthcare, California, USA.
Ostroumova, O. D., & Maksimov, M. L. (2012). Bezopasnost’ primenenija bisoprolola u bol’nyh s sochetannoj patologiej: Klinicheskaja jeffektivnost’ i jekonomicheskaja celesoobraznost’. Consilium Medicum, 14(1), 64–66 (in Russian).
Privalova, E. V. (2013). Arterial’naja gipertenzija: Zashhita organov-mishenej vs prognoz. Al’ternativnyj vybor ili zven’ja odnoj cepi? Consilium Medicum, 15(5), 14–18 (in Russian).
Roberts, C., Vaziri, N., & Wang, X. (2000). Enhanced NO inactivation and hypertension induced by a high-fat, refined-carbohydrate diet. Hypertension, 36(3), 423–429.
Ruilope, L. M. (2005). Renal function and cardiovascular risk in hypertensive patients. Journal of Hypertension, 23, 1787–1788.
Sjostrom, C. D., & Lissner, L. (1997). Relationships between changes in body composition and changes in cardiovascular risk factors: The SOS International Study. Obesity Research, 5(6), 519–530.
Stamler, R., Stamler, J., & Griim. R. (1987). Nutritional therapy for high blood pressure: Final repot of a four-year randomized controlled trial – the Hypertension Control Program. American Medical Association, 257(11), 1484–1491.
Svishhenko, E. P. (2000). Vlijanie indopresa (indapamida) na sutochnyj profil’ arterial’nogo davlenija i nejrogumoral’nye faktory ego reguljacii. Doktor, 4, 46–47 (in Russian).
Zahorska-Markiewicz, B., Janowska, J., Olszanecka-Glinianowicz, M., & Zurakowski, A. (2000). Serum concentrations of TNF-α and soluble TNF-α receptors in obesity. International Journal of Obesity, 24(11), 1392–1395.
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