Possibility of high-selective adrenoblockers use in combined therapy ofpatients with metabolic syndrome


S.N. Tolpygina

Federal State Budgetary Institution «National medical research centre of preventive medicine» of the Ministry of Healthcare of Russia, Moscow
Metabolic syndrome (MS) is widespread in the population, occuring in 10–24% of cases. Combination of cardiovascular diseases and metabolic disorders increases the risk of mortality from cardiovascular complications. Endothelial dysfunction together with hypersympathicotonia plays an imprtant role in pathophysiology of vascular diseases, arterial hypertension and cardiac insufficiency. Taking into account the important role of increased activity of sympathetiic nervous system in the development of cardiovascular diseases in case of MS, the question of possible use of β-adrenoblockers, primarily having vasodilating effect and having influence at endothelial function is actual for treatment of the certain category of patients. Nebivolol is a β-adrenoblocker with most high selectivity to β1-adrenergic receptors and causes the dilatation by increasing of nitrogen oxide production. Double mechanism of action is basing on the row of haemodynamic effects of nebivolol including heart rate and arterial pressure decrease, improve of systolic and diastolic left ventricle myocardium function. High clinical significance are having the identified advantages of nebivolol concerning metabolic profile: decrease of blood lipid level, increase of insuline sensitivity and abscence of new cases of diabetes melitus development. These advantages take place also in case of its use in MS patients. Nebivolol gives antihypertensive effect which could be compared with the same of other groups of medicaments and β-adrenoblockers, but at the same time it has a row of advantages in treatment of arterial hypertension in patients with diabetes melitus, adiposity and in elderly people in whom endothelial dysfunction is more expressed.
Keywords: nitrogen oxide, β-adrenoblockers, nebivolol, cardiovascular diseases, endothelial dysfunction, metabolic syndrome, arterial hypertension
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Literature

  • Law M.R., Morris J.K., Wald N.J. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. Br. Med. J. 2009;338:b1665.
  • Kotseva K., Wood D., De Backer G. et al. EUROASPIRE III. Management of cardiovascular risk factors in asymptomatic high-risk patients in general practice: cross-sectional survey in 12 European countries. Eur. J. Cardiovasc. Prev. Rehabil. 2010;17:530-40.
  • Basile J.N. One size does not fit all: the role of vasodilating beta-blockers in controlling hypertension as a means of reducing cardiovascular and stroke risk. Am. J. Med. 2010;123:S9–15.
  • De Caterina A.R., Leone A.M. The role of beta-blockers as first-line therapy in hypertension. Curr. Atheroscler. Rep. 2011;13:147-53.
  • Cruickshank J.M., Neil-Dwyer G., Cameron M.M. et al. Beta-adrenoreceptorblocking agents and the blood-brain barrier. Clin. Sci. 1980;59(Suppl 6):453–45.
  • Hansson L., Aberg H., Karlberg B.E. et al. Controlled study of atenolol in treatment of hypertension. Br. Med. J. 1975;5967:367-70.
  • Regеrdh C.G., Borg K.O., Johansson R. et al. Pharmacokinetic studies on the selective beta1-receptor antagonist metoprolol in man. J. Pharmacokinet. Biopharm. 1974;4:347-64.
  • Bengtsson C. The effect of metoprolol – a new selective adrenergic beta1-receptor blocking agent – in mild hypertension. Acta Med. Scand. 1976;199:65-70.
  • Sharma V., Dhillon P., Wambolt R. et al. Metoprolol improves cardiac function and modulates cardiac metabolism in the streptozotocin-diabetic rat. Am. J. Physiol. Heart Circ. Physiol. 2008;294:H1609–20.
  • Eggertsen R., Sivertsson R., Andrйn L. et al. Haemodynamic effects of carvedilol, a new beta-adrenoceptor blocker and precapillary vasodilator in essential hypertension. J. Hypertens. 1984;2:529-34.
  • Van de Water A., Janssens W., Van Neuten J. et al. Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist. J. Cardiovasc. Pharmacol. 1988;11:552-63.
  • Метелица В.И. Справочник по клинической фармакологии сердечно-сосудистых лекарственных средств. 2-е изд., перераб. и доп. М., Изд-во «БИНОМ» – СПб.: Невский диалект, 2002. 926 с. [Meteliza V.I. Handbook of clinical pharmacology of cardiovascular medicaments. 2nd edition, revised and completed. M., “BINOM”-St.Petersburg: “Nevsky dialekt”. 2002. P. 926.]
  • Janssens W.J., Geyskens D., Proost F. Comparison of the b-adrenergic antagonistic effects of Nebivolol, carvedilol, celiprolol and bisoprolol on isolated right atria and trachea of the guinea-pig. Preclinical Research Report. June 1996.
  • Fu G.S., Huang H., Chen F. et al. Carvedilol ameliorates endothelial dysfunction in streptozotocin-induced diabetic rats. Eur. J. Pharmacol. 2007;567:223–30.
  • Janssens W.J., Van de Water A., Xhonneux R. et al. Nebivolol is devoid of intrinsic sympathomimetic activity. Eur. J. Pharmacol. 1989;159:89–95.
  • Sorrentino S.A., Doerries C., Manes C. et al. Nebivolol exerts beneficial effects on endothelial function, early endothelial progenitor cells, myocardial neovascularization, and left ventricular dysfunction early after myocardial infarction beyond conventional β1-blockade. J. Am. Coll. Сardiol. 2011;57:601-11.
  • McEniery C.M., Schmitt M., Qasem A. et al. Nebivolol increases arterial distensibility in vivo. Hypertension. 2004;44:305-310.
  • Edes I., Gasior Z., Wita K. Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the ENECA study. Eur. J. Heart Fail. 2005;4:631-9.
  • Fountoulaki K., Dimopoulos V., Giannakoulis J. et al. Left ventricular mass and mechanics in mild-to-moderate hypertension: effect of nebivolol versus telmisartan. Am. J. Hypertens. 2005;18:171-7.
  • Gao Y.S., Nagao T., Bond R.A. Nebivolol induces endothelium-dependent relaxations of canine coronary arteries. J. Cardiovasc. Pharmacol. 1991;17:964-9.
  • Dubois-Rand J.L., Zelinsky R., Roudot F. et al. Effects of infusion of L-arginine into the left anterior descending coronary artery onacetylcholine-induced vasoconstriction of human atheromatous coronary arteries. Am. J. Cardiol. 1992;70:1269-75.
  • Dawes M., Brett S.E., Chowienczyk P.J. et al. The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension. Br. J. Clin. Pharmacol. 1999;48:460-3.
  • Maffei A., Di Pardo A., Carangi R. et al. Nebivolol induces nitric oxide release in the heart through inducible nitric oxide synthase activation. Hypertension. 2007;50:652-6.
  • Erdogan D., Gullu H., Caliskan M. et al. Nebivolol improves coronaryflow reserve in patients with idiopathic dilated cardiomyopathy. Heart. 2007;93:319-24.
  • Aragуn J.P., Condit M.E., Bhushan S. et al. Beta(3)-adrenoreceptor stimulation ameliorates myocardial ischemia-reperfusion injury via endothelial nitric oxide synthase and neuronal nitric oxide synthase activation. J. Am. Coll. Cardiol. 2011;58:2683-91.
  • Brehm B.R., Wolf S.C., Bertsch D. et al. Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells. Cardiovasc. Res. 2001;49:430-9.
  • Toblli J.E., Cao G., Casas G. et al. In vivo and in vitro effects of nebivolol on penile structures in hypertensive rats. Am. J. Hypertens. 2006;19:1226-32.
  • Ignjatovic V.S., Petrovic N., Miloradovic V. et al. The influence of bisoprolol dose on ADP-induced platelet aggregability in patients on dual antiplatelet therapy. Coron. Artery. Dis. 2010;21:472-6.
  • Celik T., Yuksel U.C., Iyisoy A. et al. Effects of nebivolol on platelet activation in hypertensive patients: a comparative study with metoprolol. Int. J. Cardiol. 2007;116:206-11.
  • Tuomilehto J., Wikstrand J., Olsson G. et al. Decreased coronary heart disease in hypertensive smokers. Mortality results from the MAPHY study. Hypertension. 1989;13:773-80.
  • Von Arnim T. for the TIBBS Investigators. Prognostic significance of transient ischemic episodes; response to treatment shows improved prognosis. J. Am. Coll. Cardiol 1996;28:20-4.
  • MERIT-HF Study Group. Effect of metoprolol CR/HL in chronic heart failure: metoprolol CR/HL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001-7.
  • Чазова И.Е., Мычка В.Б. Метаболический синдром. М.: Медиа Медика, 2004. [Chazova I.E., Mychka V.B. Metabolic syndrome. M.: MediaMedica,2004.]
  • Rizos E., Bairaktari E., Kostoula A. et al. The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared with that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study. J. Cardiovasc. Pharmacol. Ther. 2003;8:127-34.
  • Agabiti Rosei E., Rizzoni D. Metabolic prof ile of nebivolol,a beta adrenoceptor antagonist with unique characteristics. Drugs. 2007;67:1097-107.
  • Базиль Я.Н. Роль вазодилатирующих β-адреноблокаторов в контроле АГ и снижении риска сердечно-сосудистых и церебральных осложнений. Кардиоваскулярная терапия и профилактика. 2011;10(3):102. [Basil Ya.N. Role of vasodilatory β-adrenoblockers in blood pressure control and cardiovascular and cerebral complications risk decrease. Cardiovascular therapy and prophylaxis. 2011;10(3):102.]
  • Flather M.D., Shibata M.C., Coats A.J.S. et al. For the SENIORS Investigators. Randomized trial to determine the effect of nebivilol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur. Heart J. 2005;26:215-25.
  • Shibata M.C., Flather M.D., Wang D. Systematic review of the impact of beta blockers on mortality and hospital admissions in heart failure. Eur. J. Heart Fail. 2001;3:351-7.
  • Kamp O., Sieswerda G.T., Visser C.A. Comparison of effects on systolicand diastolic left ventricular function of nebivolol versus atenolol in patients with uncomplicated essential hypertension. Am. J. Cardiol. 2003;92:344-8.
  • Wisenbaugh T., Katz I., Davis J. et al. Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. J. Am. Coll. Cardiol. 1993;21:1094-100.
  • Uhlir O., Dvorak I., Gregor P. et al. Nebivolol in the treatment of cardiac failure: a double-blind controlled clinical trial. J. Card. Fail. 1997;3:271-76.
  • Zanchetti A. Clinical pharmacodynamics of nebivolol: new evidence of nitric oxide-mediated vasodilating activity and peculiar haemodynamic properties in hypertensive patients. Blood Press Suppl. 2004;1:17-32.
  • Nodari S., Metra M., Dei Cas L. Beta-blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective,randomized, comparison of the long-term effects of atenolol vs nebivolol. Eur. J. Heart Fail. 2003;5:621-7.
  • Brune S., Schmidt T., Tebbe U. et al. Hemodynamic effects of nebivolol at rest and on exertion in patients with heart failure. Angiology. 1990;41:696-701.
  • de Boer R.A., Doehner W., van der Horst I.C. et al SENIORS Investigators. Influence of diabetes mellitus and hyperglycemia on prognosis in patients > or =70 years old with heart failure and effects of nebivolol (data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS]). Am. J. Cardiol. 2010;106:78–86.
  • Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. Br. Med. J. 1985;291:97-104.
  • IPPPSH Collaborative Group. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). J. Hypertens. 1985;3:379-92.
  • Wilhelmsen L., Berglund G., Elmfeldt D. et al. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. J. Hypertens. 1987; 5: 561-72.
  • Wikstrand J., Warnold I., Tuomilehto J., et al. Metoprolol versus thiazide diuretics in hypertension. Morbidity results from MAPHY study. Hypertension. 1991;17:570-88.
  • Hansson L., Lindholm L., Dahlof B. et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet. 1999;354:1751-6.
  • Pepine C.J., Handberg E.M., Cooper-DeHoff R.M. et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003; 290: 2805-2816.
  • Hansson L., Hedner T., Lund-Johansen P. et al. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet 2000; 356: 359-365.
  • 2007 Guidelines for the Management of Arterial Hypertension. J. Hypertension 2007;28: 1462-36.
  • Маколкин В.И. Применение высокоселективного ß-адреноблокатора небиволола у больных метаболическим синдромом. Трудный пациент 2006, 4 №2:7-10. [Makolkin V.I.. Use of high-selective β-adrenoblocker nebivolol in metabolic syndrome patients. Difficult patient 2006, 4 № 2:7-10.]
  • De Cree J. Double blind placebo-controlled cross-over study evaluating the acute haemodynamic effects of dl-Nebivolol 5 mg, d-Nebivolol 2,5 mg an l-Nebivolol 2,5 mg in healthy volunteers. JRF Clinical Research Report on R67555 NO-35. February 1989.
  • Blankestijn P.J. Nebivolol. An acute and long term study in essential hypertension. Drug Invest 1991; 3 (suppl. 1): 152–4.
  • Jennings G. Effects of Nebivolol on haemodynamics, cardiac dimensions and function, cardiovascular reflexes and biochemical measures of sympathetic activity in normal human subjects. Drug Invest 1991; 3 (suppl. 1): 51–9.
  • Louis W.J. A study to establish the acute effects of Nebivolol on blood pressure and whether or not there are first dose postural effects in middle aged and elderly patients. Unpublished report on NEB-AUS-3, March 1995.
  • Van Rooy P. Phase I study: effects of Nebivolol 10 mg and 20 mg versus placebo on heart rate, blood pressure, systolic time intervals and side effects. A double-blind placebo-controlled cross-over study in healthy volunteers. JRF Clinical Research Report on R67555 NO-32. January 1989.
  • Zanchetti A. Trough: peak ratio of the blood pressure response to dihydropiridine calcium antagonists. J Hypertens 1994; 12 (8): S97–106.
  • Van Nueten L. Nebivolol versus nifedipine in treatment of essential hypertension: a double-blind, randomized, comparative trial. Am J Therapeutics 1998; 5: 237–43.
  • Шмидт А.С. и соавт. Гипотензивный эффект небиволола у пациентов с АГ и сахарным диабетом 2 типа. Исследование VESTONO. Кардиоваскулярная терапия и профилактика. 2010, - 9(7), - С. 1–8. [Shmidt A.S. and coauthors. Hypotensive effect of nebivolol in arterial hypertension and 2nd type diabetes melitus patients. VESTONO trial. Cardiovascular therapy and prophylaxis. 2010, - 9(7), - С. 1–8.]
  • Небиеридзе Д.В., Оганов Р.Г. Метаболические и сосудистые эффекты антигипертензивной терапии. М: Универсум Паблишинг, 2005. [Nebieridze D.V., Oganov R.G. Metabolic and vascular effects of antihypertensive therapy. M: Universum Publishing, 2005.]
  • Галявич А.С. β-Адреноблокаторы в лечении артериальной гипертонии: возможности небиволола. Consilium Medicum. 2009. Т. 9. № 5. С. 33–36. [Galyavich A.S. β-adrenoblockers in arterial hypertension treatment: capacities of nebivolol. Consilium Medicum. 2009. Т. 9. № 5. С. 33–36.]
  • Zanchetti A. Nebivolol product monograph. Milan, Italy, 2005.
  • Кириченко А.А., Миронова Е.В. Антигипертензивная эффективность и переносимость небиволола // Кардиология. 2002. № 12. С. 35–37. [Kirichenko A.A., Mironova E.V. Antihypertensive efficacy and tolerability of nebivolol//Cardiology. 2002. № 12. P. 35–37.]
  • Bakris G. Metaboliceffects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension. JAMA 2004;292:2227-36.
  • Cleophas T.J., Agrawal R., Lichtenthal A. et al. Nationwide efficacysafety study of nebivolol in mildly hypertensive patients. Am J Ther.2006;13:192–197.
  • Greathouse M. Nebivolol efficacy and safety in patients with stage I–II hypertension. Clin Cardiol. 2010;33:E20–E27.
  • Van Bortel L.M., Fici F., Mascagni F. Efficacy and tolerability of nebivolol compared with other antihypertensive drugs: a meta-analysis. Am. J. Cardiovasc. Drugs. 2008;8:35-44.
  • Vandeplassche G., Lu H.R., Wouters L. et al. Normothermic ischemic cardiac arrest in the isolated working rabbit heart: effects of dl-nebivolol and atenolol. Basic Res. Cardiol. 1991;86:21-31.
  • Van Bortel L.M., van Baak M.A. Exercise tolerance with nebivolol and atenolol. Cardiovasc. Drugs Ther. 1992;6:239-47.
  • Stoschitzky K., Stoschitzky G., Brussee H. et al. Comparing betablocking effects of bisoprolol, carvedilol and nebivolol. Cardiology. 2006;106:199-206.
  • Yilmaz M.B., Erdem A., Yalta K. et al. Impact of beta-blockers on sleep in patients with mild hypertension: a randomized trial between nebivolol and metoprolol. Adv Ther. 2008;25:871-83.
  • Cordero A., Bertomeu-Martнnez V., Mazуn P. et al. Erectile dysfunction in high-risk hypertensive patients treated with beta-blockade agents. Cardiovasc. Ther. 2010;28:15-22.
  • Van Bortel L.M., Bulpitt C.J., Fici F. Quality of life and antihypertensive effect with nebivolol and losartan. Am. J. Hypertens. 2005;18:1060-6.
  • Marazzi G., Volterrani M., Caminiti G. et al. Comparative long term effects of nebivolol and carvedilol in hypertensive heart failure patients. J. Card. Fail. 2011;17:703-9.


    • About the Autors

    Svetlana N. Tolpygina, MD, leading research worker of preventive pharmacotherapy Department of Federal State Budgetary Institution “National medical research centre of preventive medicine” of the Ministry of Healthcare of Russia. Address: 101990, Moscow, 10/3 Petroverigsky per. E-mail: stolpygina@gnicpm.ru


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