Блокаторы рецепторов к ангиотензину АII или сартаны применяются в кардиологии около 20 лет. За это время хорошо изучены особенности их влияния на ренин-ангиотензиновую систему и определено место в современной кардиологии. В статье рассматривается история создания сартанов, особенности фармакокинетики и основные фармакодинамические эффекты. Подчеркивается высокий уровень безопасности БРА, возможность их применения в комбинированной терапии. Анализируются также важные клинические эффекты саратанов, как хорошо известные (гипотензивный, нефропротективный, действие при сердечной недостаточности), так и редко рассматриваемые (нейропротекция, влияние при эректильной дисфункции и синдроме Марфана). Положительное действие БРА аргументируется клиническими исследованиями, в которых они сравниваются с другими группами кардиологических лекарственных средств. Особое внимание уделено первому препарату из группы, получившему применение в практике, – лозартану.
Angiotension II receptor blockers (ARBs) or sartans have been used in cardiology for about 20 years. For this period, their effect on the renin-angiotensin system has been well investigated and their place in modern cardiology defined. The paper considers the history of designing sartans, their pharmacokinetic features and major pharmacodynamic effects. The high level of safety of ARBs and a possibility of their use in combination therapy are underlined. The important clinical effects of sartans are also analyzed as both well-known (antihypertensive, nephroprotective ones in cardiac failure) and rarely considered (neuroprotective one in erectile dysfunction and Marfan’s syndrome). Arguments for the positive effect of ARBs are advanced by clinical studies that compare them with other groups of cardiological drugs. Particular emphasis is laid on losartan, the first medication from this group, which has found application.
1. Guidelines for the management of arterial hypertension. J Hypertens 2007; 25: 1105–87.
2. Baker KM, Johns DW, Vaughan Jr ED et al. Antihypertensive effects of angiotensin blockade: saralasin versus captopril. Clinical & Experimental Hypertension, 1980.
3. Brooke BS, Habashi JP, Judge DP et al. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med 2008; 358 (26): 2787–95.
4. Casas JP, Chua W, Loukogeorgakis S et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 2005; 366: 2026–33.
5. Dahlof B, Devereux RB, Kjeldsen SE et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 995–1003.
6. European Society of Cardiology guidelines for the management of arterial hypertension. 2003 European Society of Hypertension/Guidelines Committee. J Hypertens 2003; 21: 1011–53.
7. Ferreiro SH. History of the development of inhibitions of angiotensin I conversion. Drugs 1985; 30: 1–5.
8. Flack JM. Maximaising antihypertensive effects of angiotensin II receptor blockers with thiazide diuretic combination therapy: focus on irbesartan/hydrochlorothiazide. Int J Clin Pract 2007; 61 (12): 2093–102.
9. Kobori H, Nangaku M, Navar LG, Nishiyama A. The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease. Pharmacol Rev 2007; 59 (3): 251–87.
10. Kunz R, Friedrich C, Wolbers M, Mann JFE. Meta-analysis: Effect of Monotherapy and Combination Therapy with Inhibitors of the Renin–Angiotensin System on Proteinuria in Renal Disease. Ann Intern Med 2008; 148: 30–48.
11. Llisterri JL, Lozano Vidal JV, Aznar Vicente J et al. Sexual dysfunction in hypertensive patients treated with losartan. Am J Med Sci 2001; 321 (5): 336–41.
12. Matchar DB, McCrory DC, Orlando LA et al. Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension. Ann Intern Med 2008; 1148: 16–29.
13. Perlstein TS, Gumieniak O, Hopkins PN et al. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney Int 2004; 66: 1465–70.
14. Radonic T, de Witte P, Baars MJ et al. Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial. Trials 2010; 11 (1): 3.
15. Sica DA. Angiotensin receptor blockers: new considerations in their mechanism of action. J Clin Hypertens (Greenwich) 2006; 8 (5): 381–5.
16. Smithies O. Theodore Cooper Memorial Lecture: A mouse view of hypertension. Hypertension 1997; 30: 1318–24.
17. Takahashi S, Moriwaki Y, Yamamoto T et al. Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis 2003; 572–5.
18. Taylor W. Management of hypertension and dyslipidaemia in patients presenting with hyperuricaemia. Clin Med 2002; 80 (2): 77–8.
19. Verdecchia P, Angeli F, Repaci S et al. Comparative assessment of angiotensin receptor blockers in different clinical settings. Vasc Health Risk Manag 2009; 5: 939–48.
20. Yang R, Yang B, Wen Y et al. Losartan, an Angiotensin type I receptor, restores erectile function by downregulation of cavernous renin-angiotensin system in streptozocin-induced diabetic rats. J Sex Med 2009; 6 (3): 696–707.
21. Yusuf S, Ostergren JB, Gerstein HC et al. Effects of Candesartan on the Development of a New Diagnosis of Diabetes Mellitus in Patients With Heart Failure. Circulation 2005; 112: 48–53.
22. Барышникова Г.А. Роль блокаторов рецепторов ангиотензина в лечении артериальной гипертонии: фокус на лозартан. Систем. гипертен. 2009; 1: 26–32.
23. Национальные Рекомендации ВНОК И ОССН по диагностике и лечению ХСН (второй пересмотр). Сердеч. недостат. 2007; 8: 2.