Imidazoline receptors agonists in hypertension therapy
D.V. Nebieridze
National Medical Research Center for Preventive Medicine, Moscow
This review is devoted to a new generation sympatholytics — selective type I1-imidazoline receptor agonists (IRAs). The analysis of Russian and foreign researches convincingly testifies that this drug class provides not only adequate and long-term control of arterial blood pressure but also has a number of positive metabolic effects — it helps to reduce insulin resistance (weight loss) and has organo-protective properties (improves endothelial function, contributes to the left ventricular hypertrophy regression and microalbuminuria reduction). In this case, the IRAs are significantly less likely to cause adverse events specific to sympatholytics of the first generation. This drug class always finds its place in the Russian guidelines for the diagnosis and treatment of hypertension. The review focuses on moxonidine. The data analysis on the IRAs metabolic effects is of special interest. It is known that type I3-imidazoline receptors regulate insulin secretion with pancreatic β-cells, which causes IRAs additional effects on carbohydrate metabolism parameters. One of the mechanisms of IRAs positive influence on carbohydrate metabolism is their ability to induce the expression of insulin receptor and protein IRS-1 β-subunits in cells, which is accompanied with the improvement of the insulin signaling pathways in skeletal muscles and liver.
Keywords: imidazoline receptor agonists, insulin resistance, antihypertensive effect, metabolic effects, organo-protection.
For citation: Nebieridze D.V. Imidazoline receptors agonists in hypertension therapy. RMJ. Medical Review. 2019;1(II):83–86.
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2. Julius S. Effect of sympathetic overactivity on cardiovascular prognosis in hypertension. Eur Heart J. 1998;19(F):F14–18.
3. Bousquet P., Feldman J., Schwartz J. Central cardiovascular effects of alpha-adrenergic drugs: differences between catecholamines and imidazolines. J Pharmacol Exp Ther. 1984;230(1):232–236.
4. Parini A. Du recepteur alpha-2 adrenergique au recepteur imidazoline — guanidinique: un concept en evolution. Lettre du Pharmacol. 1989;6:3–5.
5. Небиеридзе Д.В., Бритов А.Н., Апарина Т.В. и др. Моксонидин — современный препарат выбора при артериальной гипертонии и метаболических нарушениях. Кардиология. 1999;39(1):43–47. [Nebieridze D.V., Britov A.N., Aparina T.V. et al. Moxonidine — the modern drug of choice for hypertension and metabolic disorders. Cardiology. 1999;39(1):43–47 (in Russ.)].
6. Чазова И.Е., Алмазов В.А., Шляхто Е.В. Моксонидин улучшает гликемический контроль у пациентов с артериальной гипертонией и избыточной массой тела в сравнении с метформином: исследование АЛМАЗ. Обзоры Клинической кардиологии. 2007;(9):36–47. [Chazova I.E., Almazov V.A., Shlyakhto E.V. Moxonidine improves glycemic control in patients with arterial hypertension and excess body weight in comparison with metformin: the ALMAZ study. Clinical Cardiology Reviews. 2007;(9):36–47 (in Russ.)].
7. Julius S., Gudbradson T., Jamerson K. et al. The hemodynamic link between insulin resistance and hypertension. J Hypertension. 1991;9;983–986.
8. Небиеридзе Д.В., Камышова Т.В. Агонисты имидазолиновых рецепторов: все ли мы знаем об их возможностях? Рациональная фармакотерапия в кардиологии. 2012;8(2):233–236. [Nebieridze D.V., Kamyshova T.V. Imidazoline receptor agonists: do we all know about their capabilities? Rational pharmacotherapy in cardiology. 2012;8(2):233–236 (in Russ.)].
9. Rosen P., Ohly P., Gleichmann H. Experimental benefit of moxonidine on glucose metabolism and insulin secretion in the fructose-fed rat. J Hypertens Suppl. 1997;15(1):S31–8.
10. Жернакова Ю.В., Чазова И.Е. Особенности лечения артериальной гипертонии у женщин в перименопаузе. Системные гипертензии. 2014;11(1):5–10. [Zhernakova Yu.V., Chazova I.E. Features of the treatment of arterial hypertension in perimenopausal women. Systemic hypertension. 2014;11(1):5–10 (in Russ.)].
11. Haenni A., Lithell H.O. Moxonidin improves insulin sensitivity in insulin-resistent hypertensives. J Hypertens. 1999;17(3):S29–S35.
12. Chazova I., Schlaich M.P. Improved hypertension control with the imidazoline agonist moxonidine in a multinational metabolic syndrome population: principal results of the MERSY Study. Intern J Hypertens. 2013;1–9; DOI:10.1155/2013/541689.
13. Strojek K., Grzeszczak W., Gorska J. et al. Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy? J Am Soc Nephrol. 2001;12(3):602–5.
14. Amman K., Rump L.C., Simonavicience A. et al. Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats. J Am Soc Nephrol. 2000;1:1469–78.
15. Аметов А.С., Демидова Т.Ю., Смагина Л.В. Кардио- и нефропротективные эффекты агониста имидазолиновых рецепторов моксонидина в лечении артериальной гипертензии у больных сахарным диабетом 2 типа. Сахарный диабет. 2004;7(4):8–13. [Ametov A.S., Demidova T.Yu., Smagina L.V. The cardio- and nephroprotective effects of the imidazoline receptor agonist moxonidine in the treatment of hypertension in patients with type 2 diabetes. Diabetes. 2004;7(4):8–13 (in Russ.)].
16. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105–87.
17. Krespi P.G., Makris T.K., Hatzizacharias A.N. et al. Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor — 1 levels in patients with essential hypertension. J Cardiovasc Drugs and Therapy 1998;12:463–467.
18. Национальные рекомендации по диагностике и лечению артериальной гипертонии. Кардиоваскулярная терапия и профилактика. 2008;7(6):1–36. [National guidelines for diagnosis and treatment of hypertension. Cardiovascular Therapy and Prevention. 2008;7(6):1–36 (in Russ.)].
19. Небиеридзе Д.В., Гапон Л.И., Ротарь О.П. и др. Европейские рекомендации по диагностике, лечению и профилактике артериальной гипертензии 2018 года: комментарии специалистов Российского кардиологического общества. Артериальная гипертензия. 2018;24(6):602–622. DOI:10.18705/1607–419X-2018–24–6-602–622. [Nebieridze D.V., Gapon L.I., Rotar O.P. et al. European recommendations for the diagnosis, treatment and prevention of arterial hypertension in 2018: comments of the specialists of the Russian Heart Society. Arterial hypertension. 2018;24(6):602–622. DOI: 10.18705/1607–419X-2018–24–6-602-622 (in Russ.)].
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