russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLCrussjcardiol-1521Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWВЛИЯНИЕ БЛОКАДЫ АНГИОТЕНЗИНОВЫХ РЕЦЕПТОРОВ НА ФУНКЦИЮ ЭНДОТЕЛИЯ: ФОКУС НА ОЛМЕСАРТАН МЕДОКСОМИЛEFFECT OF ANGIOTENSIN RECEPTOR BLOCKADE ON ENDOTHELIAL FUNCTION: FOCUS ON OLMESARTAN MEDOXOMILФеррариоК.FerrarioC.Центр по исследованию гипертонии и кардиоваскулярных заболеваний, Университет Вэйк Форрест, СШАUnited States2010281220100694106Copyright © Феррарио К., 20102010Феррарио К.Ferrario C.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/1521

Эндотелиальная дисфункция является связующим звеном между сердечно-сосудистыми факторами риска и начальными стадиями сердечно-сосудистого континуума, приводящего к поражению органов-мишеней. Ангиотензин II, обладающий прессорным эффектом компонент ренин-ангиотензин-альдостероновой системы, повышает артериальное давление (АД) за счет вазоконстрикции и задержки натрия и жидкости. Кроме того, ангиотензин II обладает прооксидантным действием, способствующим развитию эндотелиальной дисфункции и сосудистого ремоделирования. Блокаторы рецепторов к ангиотензину (БРА) снижают не только уровень АД, но и показатели заболеваемости и смертности у пациентов с артериальной гипертензией, гипертрофией левого желудочка, сахарным диабетом и патологией почек. Олмесартан медоксомил является эффективным, длительно действующим и хорошо переносимым БРА, который предотвращает либо способствует обратному развитию эндотелиальной дисфункции в экспериментальных моделях атеросклероза, гипертензии, диабета, нефропатии и ретинопатии у животных. Также было показано, что олмесартан медоксомил, пролекарство антигипертензив- ного препарата олмесартана, способствует уменьшению выраженности эндотелиальной дисфункции у пациентов с гипертензией или диабетом. Согласно результатам рандомизированных исследований, олмесартан медоксомил уменьшает сосудистое воспаление и объем крупных атеросклеротических бляшек, увеличивает содержание циркулирующих эндотелиальных клеток-предшественников, улучшает эндотелий-зависимую релаксацию и нормализует морфологию резистивных сосудов. Важно отметить, что влияние олмесартана медоксомила на эндотелиальную функцию считается не зависящим от гипотензивного эффекта этого препарата.

 

Endothelial dysfunction is the common link between cardiovascular disease risk factors and the earliest event in the cascade of incidents that results in target organ damage. Angiotensin II, the terminal pressor effector arm of the renin-angiotensin-aldosterone system, increases blood pressure (BP) by vasoconstriction and sodium and fluid retention, and has a prooxidative action that induces endothelial dysfunction and contributes to vascular remodeling. Angiotensin receptor blockers (ARBs) reduce BP and morbidity and mortality in patients with hypertension, ventricular hypertrophy, diabetes mellitus, and renal disease. Olmesartan medoxomil is a long-acting, well-tolerated, effective ARB that prevents or reverses endothelial dysfunction in animal models of atherosclerosis, hypertension, diabetes, nephropathy, and retinopathy. Olmesartan medoxomil, a prodrug of olmesartan approved for the treatment of hypertension, has been shown to ameliorate endothelial dysfunction in patients with hypertension or diabetes. In randomized studies, the drug reduces vascular inflammation and the volume of large atherosclerotic plaques, increases the number of regenerative endothelial progenitor cells in the peripheral circulation, improves endotheliumdependent relaxation, and restores the normal resistance vessel morphology. Importantly, the impact of olmesartan medoxomil on endothelial dysfunction is thought to be independent of BP lowering.

эндотелиальная дисфункцияблокатор рецепторов к ангиотензинуолмесартан медоксомилгипертензияатеросклерозEndothelial dysfunctionangiotensin receptor blockerolmesartan medoxomilhypertensionatherosclerosisReferencesHardoon SL, Whincup PH, Lennon LT, Wannamethee SG, Capewell S, Morris RW. How much of the recent decline in the incidence of myocardial infarction in British men can be explained by changes in cardiovascular risk factors? Evidence from a prospective populationbased study // Circulation. 2008;117(5):598–604.Hardoon SL, Whincup PH, Lennon LT, Wannamethee SG, Capewell S, Morris RW. How much of the recent decline in the incidence of myocardial infarction in British men can be explained by changes in cardiovascular risk factors? Evidence from a prospective populationbased study // Circulation. 2008;117(5):598–604.Kahn R, Robertson RM, Smith R, Eddy D. The impact of prevention on reducing the burden of cardiovascular disease // Circulation. 2008;118(5):576–585.Kahn R, Robertson RM, Smith R, Eddy D. The impact of prevention on reducing the burden of cardiovascular disease // Circulation. 2008;118(5):576–585.Perkovic V, Huxley R, Wu Y, Prabhakaran D, MacMahon S. The burden of blood pressure-related disease: a neglected priority for global health // Hypertension. 2007;50(6):991–997.Perkovic V, Huxley R, Wu Y, Prabhakaran D, MacMahon S. The burden of blood pressure-related disease: a neglected priority for global health // Hypertension. 2007;50(6):991–997.Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States // JAMA. 2007;298(17):2038–2047.Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States // JAMA. 2007;298(17):2038–2047.Fox CS, Coady S, Sorlie PD, et al. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study // Circulation. 2007;115(12):1544–1550.Fox CS, Coady S, Sorlie PD, et al. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study // Circulation. 2007;115(12):1544–1550.Kestenbaum B, Rudser KD, de Boer IH, et al. Differences in kidney function and incident hypertension: The Multi-Ethnic Study of Atherosclerosis // Ann Intern Med. 2008;148(7):501–508.Kestenbaum B, Rudser KD, de Boer IH, et al. Differences in kidney function and incident hypertension: The Multi-Ethnic Study of Atherosclerosis // Ann Intern Med. 2008;148(7):501–508.Munzel T, Sinning C, Post F, Warnholtz A, Schulz E. Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction // Ann Med. 2008;40(3):180–196.Munzel T, Sinning C, Post F, Warnholtz A, Schulz E. Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction // Ann Med. 2008;40(3):180–196.Pahkala K, Heinonen OJ, Lagstrom H, et al. Vascular endothelial function and leisure-time physical activity in adolescents // Circulation. 2008;118(23):2353–2359.Pahkala K, Heinonen OJ, Lagstrom H, et al. Vascular endothelial function and leisure-time physical activity in adolescents // Circulation. 2008;118(23):2353–2359.Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction // Circulation. 2002;106(6): 653–658.Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction // Circulation. 2002;106(6): 653–658.Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis // Circulation. 2007;115(4):459– 467.Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis // Circulation. 2007;115(4):459– 467.McAllister AS, Atkinson AB, Johnston GD, Hadden DR, Bell PM, McCance DR. Basal nitric oxide production is impaired in offspring of patients with essential hypertension // Clin Sci (Lond). 1999;97(2): 141–147.McAllister AS, Atkinson AB, Johnston GD, Hadden DR, Bell PM, McCance DR. Basal nitric oxide production is impaired in offspring of patients with essential hypertension // Clin Sci (Lond). 1999;97(2): 141–147.Schlaich MP, Parnell MM, Ahlers BA, et al. Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects // Circulation. 2004;110(24): 3680–3686.Schlaich MP, Parnell MM, Ahlers BA, et al. Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects // Circulation. 2004;110(24): 3680–3686.Yang Z, Venardos K, Jones E, Morris BJ, Chin-Dusting J, Kaye DM. Identifi cation of a novel polymorphism in the 3’UTR of the L-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction // Circulation. 2007;115(10):1269–1274.Yang Z, Venardos K, Jones E, Morris BJ, Chin-Dusting J, Kaye DM. Identifi cation of a novel polymorphism in the 3’UTR of the L-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction // Circulation. 2007;115(10):1269–1274.Zhang C. The role of infl ammatory cytokines in endothelial dysfunction // Basic Res Cardiol. 2008;103(5):398–406.Zhang C. The role of infl ammatory cytokines in endothelial dysfunction // Basic Res Cardiol. 2008;103(5):398–406.Ferrario CM, Richmond RS, Smith R, Levy P, Strawn WB, Kivlighn S. Renin-angiotensin system as a therapeutic target in managing atherosclerosis // Am J Ther. 2004;11(1):44–53.Ferrario CM, Richmond RS, Smith R, Levy P, Strawn WB, Kivlighn S. Renin-angiotensin system as a therapeutic target in managing atherosclerosis // Am J Ther. 2004;11(1):44–53.Ferrario CM, Strawn WB. Role of the renin-angiotensin-aldosterone system and proinfl ammatory mediators in cardiovascular disease // Am J Cardiol. 2006;98(1):121–128.Ferrario CM, Strawn WB. Role of the renin-angiotensin-aldosterone system and proinfl ammatory mediators in cardiovascular disease // Am J Cardiol. 2006;98(1):121–128.Strawn WB, Dean RH, Ferrario CM. Novel mechanisms linking angiotensin II and early atherogenesis // J Renin Angiotensin Aldosterone Syst. 2000;1(1):11–17.Strawn WB, Dean RH, Ferrario CM. Novel mechanisms linking angiotensin II and early atherogenesis // J Renin Angiotensin Aldosterone Syst. 2000;1(1):11–17.Strawn WB, Ferrario CM. Mechanisms linking angiotensin II and atherogenesis // Curr Opin Lipidol. 2002;13(5):505–512.Strawn WB, Ferrario CM. Mechanisms linking angiotensin II and atherogenesis // Curr Opin Lipidol. 2002;13(5):505–512.Humphrey JD. Mechanisms of arterial remodeling in hypertension: coupled roles of wall shear and intramural stress // Hypertension. 2008;52(2):195–200.Humphrey JD. Mechanisms of arterial remodeling in hypertension: coupled roles of wall shear and intramural stress // Hypertension. 2008;52(2):195–200.Abuissa H, Jones PG, Marso SP, O’Keefe JH, Jr. Angiotensinconverting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials // J Am Coll Cardiol. 2005;46(5):821–826.Abuissa H, Jones PG, Marso SP, O’Keefe JH, Jr. Angiotensinconverting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials // J Am Coll Cardiol. 2005;46(5):821–826.Schupp M, Clemenz M, Gineste R, et al. Molecular characterization of new selective peroxisome proliferator-activated receptor gamma modulators with angiotensin receptor blocking activity // Diabetes. 2005;54(12):3442–3452.Schupp M, Clemenz M, Gineste R, et al. Molecular characterization of new selective peroxisome proliferator-activated receptor gamma modulators with angiotensin receptor blocking activity // Diabetes. 2005;54(12):3442–3452.Schupp M, Lee LD, Frost N, et al. Regulation of peroxisome proliferator-activated receptor gamma activity by losartan metabolites // Hypertension. 2006;47(3):586–589.Schupp M, Lee LD, Frost N, et al. Regulation of peroxisome proliferator-activated receptor gamma activity by losartan metabolites // Hypertension. 2006;47(3):586–589.Engeli S, Bohnke J, Gorzelniak K, et al. Weight loss and the reninangiotensin- aldosterone system // Hypertension. 2005;45(3):356–362.Engeli S, Bohnke J, Gorzelniak K, et al. Weight loss and the reninangiotensin- aldosterone system // Hypertension. 2005;45(3):356–362.Engeli S, Schling P, Gorzelniak K, et al. The adipose-tissue reninangiotensin-aldosterone system: role in the metabolic syndrome? // Int J Biochem Cell Biol. 2003;35(6):807–825.Engeli S, Schling P, Gorzelniak K, et al. The adipose-tissue reninangiotensin-aldosterone system: role in the metabolic syndrome? // Int J Biochem Cell Biol. 2003;35(6):807–825.Sharma AM. Is there a rationale for angiotensin blockade in the management of obesity hypertension? // Hypertension. 2004;44(1):12– 19.Sharma AM. Is there a rationale for angiotensin blockade in the management of obesity hypertension? // Hypertension. 2004;44(1):12– 19.Sharma AM, Engeli S. The role of renin-angiotensin system blockade in the management of hypertension associated with the cardiometabolic syndrome // J Cardiometab Syndr. 2006;1(1):29–35.Sharma AM, Engeli S. The role of renin-angiotensin system blockade in the management of hypertension associated with the cardiometabolic syndrome // J Cardiometab Syndr. 2006;1(1):29–35.Varagic J, Trask AJ, Jessup JA, Chappell MC, Ferrario CM. New angiotensins // J Mol Med. 2008;86(6):663–671.Varagic J, Trask AJ, Jessup JA, Chappell MC, Ferrario CM. New angiotensins // J Mol Med. 2008;86(6):663–671.Imanishi T, Hano T, Nishio I. Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress // J Hypertens. 2005;23(1):97–104.Imanishi T, Hano T, Nishio I. Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress // J Hypertens. 2005;23(1):97–104.Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease // Circ Res. 2001;89(1): E1–E7.Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease // Circ Res. 2001;89(1): E1–E7.Strawn WB, Chappell MC, Dean RH, Kivlighn S, Ferrario CM. Inhibition of early atherogenesis by losartan in monkeys with dietinduced hypercholesterolemia // Circulation. 2000;101(13): 1586– 1593.Strawn WB, Chappell MC, Dean RH, Kivlighn S, Ferrario CM. Inhibition of early atherogenesis by losartan in monkeys with dietinduced hypercholesterolemia // Circulation. 2000;101(13): 1586– 1593.Wassmann S, Czech T, van Eickels M, Fleming I, Bohm M, Nickenig G. Inhibition of diet-induced atherosclerosis and endothelial dysfunction in apolipoprotein E/angiotensin II type 1A receptor double-knockout mice // Circulation. 2004;110(19):3062–3067.Wassmann S, Czech T, van Eickels M, Fleming I, Bohm M, Nickenig G. Inhibition of diet-induced atherosclerosis and endothelial dysfunction in apolipoprotein E/angiotensin II type 1A receptor double-knockout mice // Circulation. 2004;110(19):3062–3067.Richmond RS, Tallant EA, Gallagher PE, Ferrario CM, Strawn WB. Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells // J Renin Angiotensin Aldosterone Syst. 2004;5(4):176– 182.Richmond RS, Tallant EA, Gallagher PE, Ferrario CM, Strawn WB. Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells // J Renin Angiotensin Aldosterone Syst. 2004;5(4):176– 182.Strawn WB, Richmond RS, Ann Tallant E, Gallagher PE, Ferrario CM. Renin-angiotensin system expression in rat bone marrow haematopoietic and stromal cells // Br J Haematol. 2004;126(1):120– 126.Strawn WB, Richmond RS, Ann Tallant E, Gallagher PE, Ferrario CM. Renin-angiotensin system expression in rat bone marrow haematopoietic and stromal cells // Br J Haematol. 2004;126(1):120– 126.Strawn WB, Ferrario CM. Angiotensin II AT1 receptor blockade normalizes CD11b+ monocyte production in bone marrow of hypercholesterolemic monkeys // Atherosclerosis. 2008;196(2):624– 632.Strawn WB, Ferrario CM. Angiotensin II AT1 receptor blockade normalizes CD11b+ monocyte production in bone marrow of hypercholesterolemic monkeys // Atherosclerosis. 2008;196(2):624– 632.Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas // Proc Natl Acad Sci U S A. 2003;100(14):8258–8263.Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas // Proc Natl Acad Sci U S A. 2003;100(14):8258–8263.Santos RA, Castro CH, Gava E, et al. Impairment of in vitro and in vivo heart function in angiotensin-(1–7) receptor MAS knockout mice // Hypertension. 2006;47(5):996–1002.Santos RA, Castro CH, Gava E, et al. Impairment of in vitro and in vivo heart function in angiotensin-(1–7) receptor MAS knockout mice // Hypertension. 2006;47(5):996–1002.Castro CH, Santos RA, Ferreira AJ, Bader M, Alenina N, Almeida AP. Evidence for a functional interaction of the angiotensin-(1–7) receptor Mas with AT1 and AT2 receptors in the mouse heart // Hypertension. 2005;46(4):937–942.Castro CH, Santos RA, Ferreira AJ, Bader M, Alenina N, Almeida AP. Evidence for a functional interaction of the angiotensin-(1–7) receptor Mas with AT1 and AT2 receptors in the mouse heart // Hypertension. 2005;46(4):937–942.Dias-Peixoto MF, Santos RA, Gomes ER, et al. Molecular mechanisms involved in the angiotensin-(1–7)/Mas signaling pathway in cardiomyocytes // Hypertension. 2008;52(3):542–548.Dias-Peixoto MF, Santos RA, Gomes ER, et al. Molecular mechanisms involved in the angiotensin-(1–7)/Mas signaling pathway in cardiomyocytes // Hypertension. 2008;52(3):542–548.Gallagher PE, Ferrario CM, Tallant EA. MAP Kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides // Am J Physiol Cell Physiol. 2008;295(5): C1169–C1174.Gallagher PE, Ferrario CM, Tallant EA. MAP Kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides // Am J Physiol Cell Physiol. 2008;295(5): C1169–C1174.Sampaio WO, Henrique de Castro C, Santos RA, Schiffrin EL, Touyz RM. Angiotensin-(1–7) counterregulates angiotensin II signaling in human endothelial cells // Hypertension. 2007;50(6):1093–1098.Sampaio WO, Henrique de Castro C, Santos RA, Schiffrin EL, Touyz RM. Angiotensin-(1–7) counterregulates angiotensin II signaling in human endothelial cells // Hypertension. 2007;50(6):1093–1098.

The authors declare that there are no conflicts of interest present.