arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2009-15-3-335-341arthyper-1366Research ArticleОБЗОРREVIEWЛипотоксические эффекты в сердце, наблюдаемые при ожиренииCardiac lipotoxic effects of obesityАсташкинЕ. И.AstashkinE. I.noemail@neicon.ruГлезерМ. Г.GlezerM.cardiolog@inbox.ru <mailto:cardiolog@inbox.ru>Московская медицинская академия им. И.М. Сеченова, факультет послевузовского профессионального образования врачей, кафедра профилактической и неотложной кардиологииРоссияI.M. Sechenov Moscow Medical Academy, Faculty of Post-gradual Professional Training of Physicians, Department of the preventive and emergency cardiologyRussian Federation200928062009153335341Copyright &#x00A9; Асташкин Е.И., Глезер М.Г., 20092009Асташкин Е.И., Глезер М.Г.Astashkin E.I., Glezer M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/1366

В обзоре суммированы современные представления о «липотоксичности» и об особой форме поражения сердца, наблюдаемой при ожирении, - «липотоксической кардиомиопатии». Затронуты механизмы развития инсулинорезистентности, а также основные клинические последствия этих состояний. В статье рассматриваются основные медикаментозные подходы к коррекции данных нарушений обмена.

The review summarizes the data on lipotoxicity and lipotoxic cardiomyopathy, analyzes some mechanisms of insulin resistance and main consequences of these metabolic changes. Also the main therapeutic approaches are presented.

ожирениелипотоксичностьинсулинорезистентностьартериальная гипертонияobesitylipotoxicityinsulin resistancearterial hypertensionReferencesRahmouni K., Correia M.L.G.,. Haynes W.G et al. Obesity-associated hypertension: new insights into mechanisms // Hypertension. - 2005. - Vol. 45. - P. 9-14.Rahmouni K., Correia M.L.G.,. Haynes W.G et al. Obesity-associated hypertension: new insights into mechanisms // Hypertension. - 2005. - Vol. 45. - P. 9-14.Hall J.E. The kidney, hypertension, and obesity // Hypertension. - 2003. - Vol. 41. - P. 625-633.Hall J.E. The kidney, hypertension, and obesity // Hypertension. - 2003. - Vol. 41. - P. 625-633.Wilson P.W.F., D'Agostino R.B., Sullivan L. et al. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience // Arch. Intern. Med. - 2002. - Vol.162. - 1867-1872.Wilson P.W.F., D'Agostino R.B., Sullivan L. et al. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience // Arch. Intern. Med. - 2002. - Vol.162. - 1867-1872.Kenchaiah S., Evans J.C., Levy D. et al. Obesity and the risk of heart failure // N. Engl. J. Med. - 2002. - Vol. 347. - P. 305-313.Kenchaiah S., Evans J.C., Levy D. et al. Obesity and the risk of heart failure // N. Engl. J. Med. - 2002. - Vol. 347. - P. 305-313.Hitomi H., Kiyomoto H., Nishiyama A. Angiotensin II and oxidative stress // Curr. Opin. Cardiol. - 2007. - Vol. 22. - P. 311-315.Hitomi H., Kiyomoto H., Nishiyama A. Angiotensin II and oxidative stress // Curr. Opin. Cardiol. - 2007. - Vol. 22. - P. 311-315.Zhou Y.T., Grayburn P., Karim A. et al. Lipotoxic heart disease in obese rats: implications for human obesity // Proc. Natl. Acad. Sci. - 2000. - Vol. 97. - P. 1784-1789.Zhou Y.T., Grayburn P., Karim A. et al. Lipotoxic heart disease in obese rats: implications for human obesity // Proc. Natl. Acad. Sci. - 2000. - Vol. 97. - P. 1784-1789.Chiu H.C., Kovacs A., Ford D.A. et al. A novel mouse model of lipotoxic cardiomyopathy // J. Clin. Invest. - 2001. - Vol. 107. - P. 813-822.Chiu H.C., Kovacs A., Ford D.A. et al. A novel mouse model of lipotoxic cardiomyopathy // J. Clin. Invest. - 2001. - Vol. 107. - P. 813-822.Асташкин Е.И., Глезер М.Г. Фармакологическая регуляция обмена энергетических субстратов в кардиомиоцитах при патологических состояниях, связанных с ишемией // Кардиоваск. тер. и профилактика. - 2006. - T. 5, № 7. - C. 112-123.Асташкин Е.И., Глезер М.Г. Фармакологическая регуляция обмена энергетических субстратов в кардиомиоцитах при патологических состояниях, связанных с ишемией // Кардиоваск. тер. и профилактика. - 2006. - T. 5, № 7. - C. 112-123.Finck B.N. The role of the peroxisome proliferator-activated receptor-alpha pathway in pathological remodeling of the diabetic heart // Curr. Opin. Clin. Nutr. Metab. Care. - 2004. - Vol. 7. - P. 391-396.Finck B.N. The role of the peroxisome proliferator-activated receptor-alpha pathway in pathological remodeling of the diabetic heart // Curr. Opin. Clin. Nutr. Metab. Care. - 2004. - Vol. 7. - P. 391-396.Pillutla P., Hwang Y.C., Augustus A. et al. Perfusion of hearts with triglyceride-rich particles reproduces the metabolic abnormalities in lipotoxic cardiomyopathy // Am. J. Physiol. Endocrinol. Metab. - 2005. - Vol. 288. P. E1229-E1235.Pillutla P., Hwang Y.C., Augustus A. et al. Perfusion of hearts with triglyceride-rich particles reproduces the metabolic abnormalities in lipotoxic cardiomyopathy // Am. J. Physiol. Endocrinol. Metab. - 2005. - Vol. 288. P. E1229-E1235.Chiu H.C., Kovacs A., Blanton R.M. et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy // Circ. Res. - 2005. - Vol. 96. - P. 225-233.Chiu H.C., Kovacs A., Blanton R.M. et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy // Circ. Res. - 2005. - Vol. 96. - P. 225-233.Yagyu H., Chen G., Yokoyama M. et al. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy // J. Clin. Invest. - 2003. - Vol. 111. - P. 419-426.Yagyu H., Chen G., Yokoyama M. et al. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy // J. Clin. Invest. - 2003. - Vol. 111. - P. 419-426.Petersen K.F., Befroy D., Dufour S. et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance // Science. - 2003. - Vol. 300. - P. 1140-1142.Petersen K.F., Befroy D., Dufour S. et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance // Science. - 2003. - Vol. 300. - P. 1140-1142.Petersen K.F., Dufour S., Befroy D. et al. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes // N. Engl. J. Med. - 2004. - Vol. 350. - P. 664-671.Petersen K.F., Dufour S., Befroy D. et al. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes // N. Engl. J. Med. - 2004. - Vol. 350. - P. 664-671.Unger R.H. Lipotoxic diseases // Annu. Rev. Med. - 2002. - Vol. 53. - P. 319-336.Unger R.H. Lipotoxic diseases // Annu. Rev. Med. - 2002. - Vol. 53. - P. 319-336.Leone T.C., Weinheimer C.J., Kelly D.P. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders // Proc. Natl. Acad. Sci. U S A. - 1999. - Vol. 96. - P. 7473-7478.Leone T.C., Weinheimer C.J., Kelly D.P. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders // Proc. Natl. Acad. Sci. U S A. - 1999. - Vol. 96. - P. 7473-7478.Watanabe K., Fujii H., Takahashi T. et al. Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age dependent cardiac toxicity // J. Biol. Chem. - 2000. - Vol. 275. - P. 22293-22299.Watanabe K., Fujii H., Takahashi T. et al. Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age dependent cardiac toxicity // J. Biol. Chem. - 2000. - Vol. 275. - P. 22293-22299.Kelly L.J., Vicario P.P., Thompson G.M. et al. Peroxisome proliferator-activated receptors gamma and alpha mediate in vivo regulation of uncoupling protein (UCP-1, UCP-2, UCP-3) gene expression // Endocrinology. - 1998. - Vol. 139. - P. 4920-4927.Kelly L.J., Vicario P.P., Thompson G.M. et al. Peroxisome proliferator-activated receptors gamma and alpha mediate in vivo regulation of uncoupling protein (UCP-1, UCP-2, UCP-3) gene expression // Endocrinology. - 1998. - Vol. 139. - P. 4920-4927.Djouadi F., Brandt J.M., Weinheimer C.J. et al. The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism // Prostaglandins Leukot. Essent. Fatty Acids. - 1999. - Vol. 60. - P. 339-343.Djouadi F., Brandt J.M., Weinheimer C.J. et al. The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism // Prostaglandins Leukot. Essent. Fatty Acids. - 1999. - Vol. 60. - P. 339-343.Finck B.N., Lehman J.J., Leone T.C. et al. The cardiac phenotype induced by PPAR-alpha overexpression mimics that caused by diabetes mellitus // J. Clin. Invest. - 2002. - Vol. 109. - P. 121-130.Finck B.N., Lehman J.J., Leone T.C. et al. The cardiac phenotype induced by PPAR-alpha overexpression mimics that caused by diabetes mellitus // J. Clin. Invest. - 2002. - Vol. 109. - P. 121-130.Yang J., Sambandam N., Han X., Gross R.W. et al. CD36 deficiency rescues lipotoxic cardiomyopathy // Circ. Res. - 2007. - Vol. 100. - P. 1208-1217.Yang J., Sambandam N., Han X., Gross R.W. et al. CD36 deficiency rescues lipotoxic cardiomyopathy // Circ. Res. - 2007. - Vol. 100. - P. 1208-1217.Buchanan J., Mazumder P.K., Hu P. et al. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity // Endocrinology. - 2005. - Vol. 146. - P. 5341-5349.Buchanan J., Mazumder P.K., Hu P. et al. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity // Endocrinology. - 2005. - Vol. 146. - P. 5341-5349.Christoffersen C., Bollano E., Lindegaard M.L. et al. Cardiac lipid accumulation associated withdiastolic dysfunction in obese mice // Endocrinology. - 2003. - Vol. 144. - P. 3483-3490.Christoffersen C., Bollano E., Lindegaard M.L. et al. Cardiac lipid accumulation associated withdiastolic dysfunction in obese mice // Endocrinology. - 2003. - Vol. 144. - P. 3483-3490.Vikramadithyan R.K., Hirata K., Yagyu H. et al. Peroxisome proliferator-activated receptor agonists modulate heart function in transgenic mice with lipotoxic cardiomyopathy // J. Pharmacol. Exp. Ther. - 2005. - Vol. 313. - P. 586-593.Vikramadithyan R.K., Hirata K., Yagyu H. et al. Peroxisome proliferator-activated receptor agonists modulate heart function in transgenic mice with lipotoxic cardiomyopathy // J. Pharmacol. Exp. Ther. - 2005. - Vol. 313. - P. 586-593.Lee Y., Naseem R.H., Duplomb L. et al. Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice // Proc. Natl. Acad. Sci. U S A. - 2004. - Vol. 101. - P. 13624-13629.Lee Y., Naseem R.H., Duplomb L. et al. Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice // Proc. Natl. Acad. Sci. U S A. - 2004. - Vol. 101. - P. 13624-13629.Barouch L.A., Gao D., Chen L. et al. Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity // Circ. Res. - 2006. - Vol. 98. - P. 119-124.Barouch L.A., Gao D., Chen L. et al. Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity // Circ. Res. - 2006. - Vol. 98. - P. 119-124.Cai L., Li W., Wang G. et al. Hyperglycemia induced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway // Diabetes. - 2002. - Vol. 51. - P. 1938-1948.Cai L., Li W., Wang G. et al. Hyperglycemia induced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway // Diabetes. - 2002. - Vol. 51. - P. 1938-1948.Dyntar D., Eppenberger-Eberhardt M., Maedler K. et al. Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes // Diabetes. - 2001. - Vol. 50. - P. 2105-2113.Dyntar D., Eppenberger-Eberhardt M., Maedler K. et al. Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes // Diabetes. - 2001. - Vol. 50. - P. 2105-2113.Hickson-Bick D.L., Buja M.L., McMillin J.B. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes // J. Mol. Cell. Cardiol. - 2000. - Vol. 32. - P. 511-519.Hickson-Bick D.L., Buja M.L., McMillin J.B. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes // J. Mol. Cell. Cardiol. - 2000. - Vol. 32. - P. 511-519.Unger R.H., Orci L. Lipoapoptosis: its mechanism and its diseases // Biochim. Biophys. Acta. - 2002. - Vol. 1585. - P. 202-212.Unger R.H., Orci L. Lipoapoptosis: its mechanism and its diseases // Biochim. Biophys. Acta. - 2002. - Vol. 1585. - P. 202-212.Ghafourifar P., Klein S.D., Schucht O. et al. Ceramide induces cytochrome С release from isolated mitochondria. Importance of mitochondrial redox state // J. Biol. Chem. - 1999. - Vol. 274. - P. 6080-6084.Ghafourifar P., Klein S.D., Schucht O. et al. Ceramide induces cytochrome С release from isolated mitochondria. Importance of mitochondrial redox state // J. Biol. Chem. - 1999. - Vol. 274. - P. 6080-6084.Ostrander D.B., Sparagna G.C., Amoscato A.A. et al. Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis // J. Biol. Chem. - 2001. - Vol. 276. - P. 38061-38067.Ostrander D.B., Sparagna G.C., Amoscato A.A. et al. Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis // J. Biol. Chem. - 2001. - Vol. 276. - P. 38061-38067.Rui L., Aguirre V., Kim J.K. et al. Insulin/IGF1 and TNFalpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways // J. Clin. Invest. - 2001. - Vol. 107. - P. 181-189.Rui L., Aguirre V., Kim J.K. et al. Insulin/IGF1 and TNFalpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways // J. Clin. Invest. - 2001. - Vol. 107. - P. 181-189.Kim J.K., Fillmore J.J., Sunshine M.J. et al. PKC-theta knockout mice are protected from fat-induced insulin resistance // J. Clin. Invest. - 2004. - Vol. 114. - P. 823-827.Kim J.K., Fillmore J.J., Sunshine M.J. et al. PKC-theta knockout mice are protected from fat-induced insulin resistance // J. Clin. Invest. - 2004. - Vol. 114. - P. 823-827.Yuan M., Konstantopoulos N., Lee J. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IkB-beta // Science. - 2001. - Vol. 293. - P. 1673-1677.Yuan M., Konstantopoulos N., Lee J. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IkB-beta // Science. - 2001. - Vol. 293. - P. 1673-1677.Sharma S., Adrogue J.V., Golfman L. et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart // FASEB J. - 2004. - Vol. 18. - P. 1692-1700.Sharma S., Adrogue J.V., Golfman L. et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart // FASEB J. - 2004. - Vol. 18. - P. 1692-1700.Gottdiener M.D., Reda M.S., Williams M.S. et al. Left atrial size in hypertensive men: influence of obesity, race and age // J. Am. Coll. Cardiol. - 1997. - Vol. 29. - P. 651-658.Gottdiener M.D., Reda M.S., Williams M.S. et al. Left atrial size in hypertensive men: influence of obesity, race and age // J. Am. Coll. Cardiol. - 1997. - Vol. 29. - P. 651-658.Savage D.D., Garrison R.J., Kannel W.B. et al. The spectrum of left ventricular hypertrophy in a general population sample: the Framingham Study // Circulation. - 1987. - Vol. 75 (suppl. I). - P. I-26-I-33.Savage D.D., Garrison R.J., Kannel W.B. et al. The spectrum of left ventricular hypertrophy in a general population sample: the Framingham Study // Circulation. - 1987. - Vol. 75 (suppl. I). - P. I-26-I-33.Hammond I.W., Devereux R.B., Alderman M.H. et al. Relation of blood pressure and body build to left ventricular mass in normotensive and hypertensive employed adults // J. Am. Coll. Cardiol. - 1988. - Vol. 12. - P. 996-1004.Hammond I.W., Devereux R.B., Alderman M.H. et al. Relation of blood pressure and body build to left ventricular mass in normotensive and hypertensive employed adults // J. Am. Coll. Cardiol. - 1988. - Vol. 12. - P. 996-1004.Messerli F.H., Sundgaard-Rise K., Reisen E.D. et al. Dimorphic cardiac adaptation to obesity and arterial hypertension //Ann. Intern. Med. - 1983. - Vol. 99. - P. 757-761.Messerli F.H., Sundgaard-Rise K., Reisen E.D. et al. Dimorphic cardiac adaptation to obesity and arterial hypertension //Ann. Intern. Med. - 1983. - Vol. 99. - P. 757-761.Levy D., Anderson K.M., Savage D.D. et al. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study // Ann. Intern. Med. - 1988. - Vol. 108. - P. 7-13.Levy D., Anderson K.M., Savage D.D. et al. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study // Ann. Intern. Med. - 1988. - Vol. 108. - P. 7-13.Garavaglia G.E., Messerli F.H., Nunez B.D. et al. Myocardial contractility and left ventricular function in obese patients with essential hypertension // Am. J. Cardiol. - 1988. - Vol. 62. - P. 594-597.Garavaglia G.E., Messerli F.H., Nunez B.D. et al. Myocardial contractility and left ventricular function in obese patients with essential hypertension // Am. J. Cardiol. - 1988. - Vol. 62. - P. 594-597.De Simone G., Devereux R.B., Roman M.J. et al. Relation of Obesity and Gender to Left Ventricular Hypertrophy in Normotensive and Hypertensive Adults // Hypertension. - 1994. - Vol. 23. - P. 600-606.De Simone G., Devereux R.B., Roman M.J. et al. Relation of Obesity and Gender to Left Ventricular Hypertrophy in Normotensive and Hypertensive Adults // Hypertension. - 1994. - Vol. 23. - P. 600-606.Ganau A., Devereux R.B., Pickering T.G. et al. Relation of left ventricular hemodynamic load and contractile performance to left ventricular mass in hypertension // Circulation. - 1990. - Vol. 81. - P. 25-36.Ganau A., Devereux R.B., Pickering T.G. et al. Relation of left ventricular hemodynamic load and contractile performance to left ventricular mass in hypertension // Circulation. - 1990. - Vol. 81. - P. 25-36.Alexander J.K. Obesity and the circulation // Mod. Concepts Cardiovasc. Dis. - 1963. - Vol. 32. - P. 799-803.Alexander J.K. Obesity and the circulation // Mod. Concepts Cardiovasc. Dis. - 1963. - Vol. 32. - P. 799-803.De Simone G., Devereux R.B. Hemorheologic abnormalities in obesity: hemodynamic and prognostic implications // Nutr. Metab. Cardiovasc. Dis. - 1992. - Vol. 2. - P. 185-190.De Simone G., Devereux R.B. Hemorheologic abnormalities in obesity: hemodynamic and prognostic implications // Nutr. Metab. Cardiovasc. Dis. - 1992. - Vol. 2. - P. 185-190.De Simone G., Devereux R.B., Roman M.J. et al. Gender differences in left ventricular anatomy, blood viscosity and volume regulatory hormones in normal adults // Am. J. Cardiol. -1991. - Vol. 68. - P. 1704-1708.De Simone G., Devereux R.B., Roman M.J. et al. Gender differences in left ventricular anatomy, blood viscosity and volume regulatory hormones in normal adults // Am. J. Cardiol. -1991. - Vol. 68. - P. 1704-1708.Lauer M.S., Anderson K.M., Kannel W.B. et al. The impact of obesity on left ventricular mass and geometry: the Framingham Heart Study // JAMA. - 1991. - Vol. 2666. - P. 231-236.Lauer M.S., Anderson K.M., Kannel W.B. et al. The impact of obesity on left ventricular mass and geometry: the Framingham Heart Study // JAMA. - 1991. - Vol. 2666. - P. 231-236.Frustaci A., Kajstura J., Chimenti C. et al. Myocardial cell death in human diabetes // Circ. Res. - 2000. - Vol. 87. - P. 1123-1132.Frustaci A., Kajstura J., Chimenti C. et al. Myocardial cell death in human diabetes // Circ. Res. - 2000. - Vol. 87. - P. 1123-1132.Scheuermann-Freestone M., Madsen P.L., Manners D. et al. Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes // Circulation. - 2003. - Vol. 107. - P. 3040-3046.Scheuermann-Freestone M., Madsen P.L., Manners D. et al. Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes // Circulation. - 2003. - Vol. 107. - P. 3040-3046.Yanovski S.Z., Yanovski J.A.Y. Obesity // N. Engl. J. Med. - 2002. - Vol. 346, № 8. - P. 591-602.Yanovski S.Z., Yanovski J.A.Y. Obesity // N. Engl. J. Med. - 2002. - Vol. 346, № 8. - P. 591-602.Day C., Bailey C.J. Sibutramine update // Br. J. Diabet. Vasc. Dis. - 2002. - Vol. 2. - P. 392-397.Day C., Bailey C.J. Sibutramine update // Br. J. Diabet. Vasc. Dis. - 2002. - Vol. 2. - P. 392-397.James W.P., Astrup A., Finer N. et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance // Lancet. - 2000. - Vol. 356. - P. 2119-2125.James W.P., Astrup A., Finer N. et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance // Lancet. - 2000. - Vol. 356. - P. 2119-2125.Torp-Pedersen C., Caterson I., Coutinho W. et al. SCOUT Investigators. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial // Eur. Heart J. - 2007. - Vol. 28, № 23. - P. 2915-2923.Torp-Pedersen C., Caterson I., Coutinho W. et al. SCOUT Investigators. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial // Eur. Heart J. - 2007. - Vol. 28, № 23. - P. 2915-2923.Rett J.K., Henriksen E.K. Antihypertensive therapy and insulin sensitivity: Do we have to redefine the role of beta-blocking agents? // Am. J. Hypertension. - 1998. - Vol. 11, № 10. - P. 1258-1265.Rett J.K., Henriksen E.K. Antihypertensive therapy and insulin sensitivity: Do we have to redefine the role of beta-blocking agents? // Am. J. Hypertension. - 1998. - Vol. 11, № 10. - P. 1258-1265.Kaaja R ., Kujala S ., Manhem K . et al. Effects of sympatholytic therapy on insulin sensitivity indices in hypertensive postmenopausal women // Int. J. Clin. Pharmacol. Ther. - 2007. - Vol. 45, № 7. - P. 394-401.Kaaja R ., Kujala S ., Manhem K . et al. Effects of sympatholytic therapy on insulin sensitivity indices in hypertensive postmenopausal women // Int. J. Clin. Pharmacol. Ther. - 2007. - Vol. 45, № 7. - P. 394-401.Kuperstein R., Sasson Z . Effects of antihypertensive therapy on glucose and insulin metabolism and on left ventricular mass: A randomized, double-blind, controlled study of 21 obese hypertensives // Circulation. - 2000. - Vol. 102, № 15. - P. 1802-1806.Kuperstein R., Sasson Z . Effects of antihypertensive therapy on glucose and insulin metabolism and on left ventricular mass: A randomized, double-blind, controlled study of 21 obese hypertensives // Circulation. - 2000. - Vol. 102, № 15. - P. 1802-1806.Halperin A.K ., Cubeddu L.X. The role of calcium channel blockers in the treatment of hypertension // Am. Heart. J. - 1986. - Vol. 111, № 2. - P. 363-382.Halperin A.K ., Cubeddu L.X. The role of calcium channel blockers in the treatment of hypertension // Am. Heart. J. - 1986. - Vol. 111, № 2. - P. 363-382.McAllister R.G.Jr . Clinical pharmacology of slow channel blocking agents // Prog. Cardiovasc. Dis. - 1982. - Vol. 25, № 2. - P. 83-100.McAllister R.G.Jr . Clinical pharmacology of slow channel blocking agents // Prog. Cardiovasc. Dis. - 1982. - Vol. 25, № 2. - P. 83-100.Binggeli C ., Corti R., Sudano I . et al. Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension // Hypertension . - 2002. - Vol. 39, № 4. - P. 892-896.Binggeli C ., Corti R., Sudano I . et al. Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension // Hypertension . - 2002. - Vol. 39, № 4. - P. 892-896.Lefrandt J.D ., Heitmann J., Sevre K . et al. The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study // Am. J. Hypertens. - 2001. - Vol. 14 (11 Pt 1). - P. 1083-1089.Lefrandt J.D ., Heitmann J., Sevre K . et al. The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study // Am. J. Hypertens. - 2001. - Vol. 14 (11 Pt 1). - P. 1083-1089.Jamerson K., Bakris G.L., Dahlöf B. et al. ACCOMPLISH Investigators. Exceptional early blood pressure control rates: the ACCOMPLISH trial // Blood Press. - 2007. - Vol. 16. - P. 80-86.Jamerson K., Bakris G.L., Dahlöf B. et al. ACCOMPLISH Investigators. Exceptional early blood pressure control rates: the ACCOMPLISH trial // Blood Press. - 2007. - Vol. 16. - P. 80-86.Nakou E ., Filippatos T.D., Liberopoulos E.N . et al. Effects of sibutramine plus verapamil sustained release/trandolapril combination on blood pressure and metabolic variables in obese hypertensive patients // Expert Opin. Pharmacother. - 2008. - Vol. 9, № 10. - P. 1629-1639.Nakou E ., Filippatos T.D., Liberopoulos E.N . et al. Effects of sibutramine plus verapamil sustained release/trandolapril combination on blood pressure and metabolic variables in obese hypertensive patients // Expert Opin. Pharmacother. - 2008. - Vol. 9, № 10. - P. 1629-1639.Scholze J ., Grimm E., Herrmann D . et al. Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study // Circulation. - 2007. - Vol. 115, № 15. - P. 1991-1998.Scholze J ., Grimm E., Herrmann D . et al. Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study // Circulation. - 2007. - Vol. 115, № 15. - P. 1991-1998.

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