Clinical Significance of Endothelial Dysfunction in Essential Hypertension (original) (raw)

• Fishman AP. Endothelium: a distributed organ of diverse capabilities. Ann N Y Acad Sci. 1982;401:1–8.
  Article CAS PubMed Google Scholar
• Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315(17):1046–51.
  Article CAS PubMed Google Scholar
• Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340(8828):1111–5. A innovative study where Celermajer et al described the first non-invasive methodology of endothelial function assessment.
  Article CAS PubMed Google Scholar
• Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertension Rep. 2010;12(6):448–55.
  Article Google Scholar
• Gkaliagkousi E, Ritter J, Ferro A. Platelet-derived nitric oxide signaling and regulation. Circ Res. 2007;101(7):654–62.
  Article CAS PubMed Google Scholar
• Palmer RM, Rees DD, Ashton DS, Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988;153(3):1251–6.
  Article CAS PubMed Google Scholar
• Piazza M, Futrega K, Spratt DE, Dieckmann T, Guillemette JG. Structure and dynamics of calmodulin (CaM) bound to nitric oxide synthase peptides: effects of a phosphomimetic CaM mutation. Biochemistry. 2012;51(17):3651–61.
  Article CAS PubMed Google Scholar
• Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, Busse R. Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res. 2001;88(11):E68–75.
  Article CAS PubMed Google Scholar
• Fleming I, Bauersachs J, Busse R. Calcium-dependent and calcium-independent activation of the endothelial NO synthase. J Vasc Res. 1997;34(3):165–74.
  Article CAS PubMed Google Scholar
• Gkaliagkousi E, Douma S, Zamboulis C, Ferro A. Nitric oxide dysfunction in vascular endothelium and platelets: role in essential hypertension. J Hypertens. 2009;27(12):2310–20.
  Article CAS PubMed Google Scholar
• Fleming I, Busse R. Signal transduction of eNOS activation. Cardiovasc Res. 1999;43(3):532–41.
  Article CAS PubMed Google Scholar
• List BM, Klosch B, Volker C, Gorren AC, Sessa WC, Werner ER, et al. Characterization of bovine endothelial nitric oxide synthase as a homodimer with down-regulated uncoupled NADPH oxidase activity: tetrahydrobiopterin binding kinetics and role of haem in dimerization. Biochem J. 1997;323(Pt 1):159–65.
  Article PubMed Central CAS PubMed Google Scholar
• Bevers LM, Braam B, Post JA, van Zonneveld AJ, Rabelink TJ, Koomans HA, et al. Tetrahydrobiopterin, but not L-arginine, decreases NO synthase uncoupling in cells expressing high levels of endothelial NO synthase. Hypertension. 2006;47(1):87–94.
  Article CAS PubMed Google Scholar
• Gkaliagkousi E, Passacquale G, Douma S, Zamboulis C, Ferro A. Platelet activation in essential hypertension: implications for antiplatelet treatment. Am J Hypertens. 2010;23(3):229–36.
  Article CAS PubMed Google Scholar
• Gkaliagkousi E, Corrigall V, Becker S, de Winter P, Shah A, Zamboulis C, et al. Decreased platelet nitric oxide contributes to increased circulating monocyte-platelet aggregates in hypertension. Eur Heart J. 2009;30(24):3048–54. An original study linking decreased NO bioavailability with platelet activation in essential hypertension.
  Article CAS PubMed Google Scholar
• Gkaliagkousi E, Gavriilaki E, Yiannaki E, Markala D, Papadopoulos N, Triantafyllou A, et al. Platelet activation in essential hypertension during exercise: pre- and post-treatment changes with an angiotensin II receptor blocker. Am J Hypertens. 2014;27(4):571–8.
  Article CAS PubMed Google Scholar
• Lekakis J, Abraham P, Balbarini A, Blann A, Boulanger CM, Cockcroft J, et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil Off J Eur Soc Cardiol Working Groups Epidemiol Prev Cardiac Rehabil Exerc Physiol. 2011;18(6):775–89. A position statement summarising current markers of endothelial dysfunction.
  Google Scholar
• Horowitz JD, Heresztyn T. An overview of plasma concentrations of asymmetric dimethylarginine (ADMA) in health and disease and in clinical studies: methodological considerations. J Chromatogr B Anal Technol Biomed Life Sci. 2007;851(1-2):42–50.
  Article CAS Google Scholar
• Perticone F, Sciacqua A, Maio R, Perticone M, Maas R, Boger RH, et al. Asymmetric dimethylarginine, L-arginine, and endothelial dysfunction in essential hypertension. J Am Coll Cardiol. 2005;46(3):518–23.
  Article CAS PubMed Google Scholar
• Juonala M, Viikari JS, Alfthan G, Marniemi J, Kahonen M, Taittonen L, et al. Brachial artery flow-mediated dilation and asymmetrical dimethylarginine in the cardiovascular risk in young Finns study. Circulation. 2007;116(12):1367–73.
  Article PubMed Google Scholar
• Boger RH, Maas R, Schulze F, Schwedhelm E. Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality--an update on patient populations with a wide range of cardiovascular risk. Pharmacol Res Off J Italian Pharmacol Soc. 2009;60(6):481–7.
  Article Google Scholar
• Boger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, et al. Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation. 2009;119(12):1592–600. A large community-based study correlating ADMA with cardiovascular morbidity and mortality.
  Article PubMed Central PubMed Google Scholar
• Dignat-George F, Boulanger CM. The many faces of endothelial microparticles. Arterioscler Thromb Vasc Biol. 2011;31(1):27–33.
  Article CAS PubMed Google Scholar
• Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension. 2006;48(2):180–6.
  Article CAS PubMed Google Scholar
• Amabile N, Cheng S, Renard JM, Larson MG, Ghorbani A, McCabe E, et al. Association of circulating endothelial microparticles with cardiometabolic risk factors in the Framingham Heart Study. Eur Heart J. 2014;35(42):2972–9.
  Article PubMed Google Scholar
• Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126(6):753–67.
  Article PubMed Central PubMed Google Scholar
• Muiesan ML, Salvetti M, Monteduro C, Corbellini C, Guelfi D, Rizzoni D, et al. Flow-mediated dilatation of the brachial artery and left ventricular geometry in hypertensive patients. J Hypertens. 2001;19(3 Pt 2):641–7.
  Article CAS PubMed Google Scholar
• Clarkson P, Celermajer DS, Donald AE, Sampson M, Sorensen KE, Adams M, et al. Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. J Am Coll Cardiol. 1996;28(3):573–9.
  Article CAS PubMed Google Scholar
• Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 1993;88(5 Pt 1):2149–55.
  Article CAS PubMed Google Scholar
• Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24(6):1468–74.
  Article CAS PubMed Google Scholar
• Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26(5):1235–41.
  Article CAS PubMed Google Scholar
• Halcox JP, Donald AE, Ellins E, Witte DR, Shipley MJ, Brunner EJ, et al. Endothelial function predicts progression of carotid intima-media thickness. Circulation. 2009;119(7):1005–12.
  Article PubMed Google Scholar
• Yeboah J, Crouse JR, Bluemke DA, Lima JA, Polak JF, Burke GL, et al. Endothelial dysfunction is associated with left ventricular mass (assessed using MRI) in an adult population (MESA). J Hum Hypertens. 2011;25(1):25–31.
  Article PubMed Central CAS PubMed Google Scholar
• Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007;115(18):2390–7.
  Article PubMed Google Scholar
• Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120(6):502–9.
  Article PubMed Central PubMed Google Scholar
• Huang AL, Silver AE, Shvenke E, Schopfer DW, Jahangir E, Titas MA, et al. Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery. Arterioscler Thromb Vasc Biol. 2007;27(10):2113–9.
  Article PubMed Central CAS PubMed Google Scholar
• Hafner F, Kieninger A, Meinitzer A, Gary T, Froehlich H, Haas E, et al. Endothelial dysfunction and brachial intima-media thickness: long term cardiovascular risk with claudication related to peripheral arterial disease: a prospective analysis. PLoS One. 2014;9(4):e93357.
  Article PubMed Central PubMed Google Scholar
• Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002;40(3):505–10.
  Article PubMed Google Scholar
• Takishima I, Nakamura T, Hirano M, Kitta Y, Kobayashi T, Fujioka D, et al. Predictive value of serial assessment of endothelial function in chronic heart failure. Int J Cardiol. 2012;158(3):417–22.
  Article PubMed Google Scholar
• Yang Y, Xu JZ, Wang Y, Tang XF, Gao PJ. Brachial flow-mediated dilation predicts subclinical target organ damage progression in essential hypertensive patients: a 3-year follow-up study. J Hypertens. 2014;32(12):2393–400. discussion 2400. A prospective study implicating FMD as an early marker of subclinical target organ damage in patients with essential hypertension.
  Article CAS PubMed Google Scholar
• Laurent S, Briet M, Boutouyrie P. Large and small artery cross-talk and recent morbidity-mortality trials in hypertension. Hypertension. 2009;54(2):388–92.
  Article CAS PubMed Google Scholar
• Ott C, Raff U, Harazny JM, Michelson G, Schmieder RE. Central pulse pressure is an independent determinant of vascular remodeling in the retinal circulation. Hypertension. 2013;61(6):1340–5.
  Article CAS PubMed Google Scholar
• Triantafyllou A, Anyfanti P, Gavriilaki E, Zabulis X, Gkaliagkousi E, Petidis K, et al. Association between retinal vessel caliber and arterial stiffness in a population comprised of normotensive to early-stage hypertensive individuals. Am J Hypertens. 2014;27(12):1472–8.
  Article PubMed Google Scholar
• Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR. Nitric oxide regulates local arterial distensibility in vivo. Circulation. 2002;105(2):213–7.
  Article CAS PubMed Google Scholar
• Schmitt M, Avolio A, Qasem A, McEniery CM, Butlin M, Wilkinson IB, et al. Basal NO locally modulates human iliac artery function in vivo. Hypertension. 2005;46(1):227–31.
  Article CAS PubMed Google Scholar
• Stewart AD, Millasseau SC, Kearney MT, Ritter JM, Chowienczyk PJ. Effects of inhibition of basal nitric oxide synthesis on carotid-femoral pulse wave velocity and augmentation index in humans. Hypertension. 2003;42(5):915–8.
  Article CAS PubMed Google Scholar
• Nigam A, Mitchell GF, Lambert J, Tardif JC. Relation between conduit vessel stiffness (assessed by tonometry) and endothelial function (assessed by flow-mediated dilatation) in patients with and without coronary heart disease. Am J Cardiol. 2003;92(4):395–9.
  Article PubMed Google Scholar
• Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588–605.
  Article PubMed Google Scholar
• Kobayashi K, Akishita M, Yu W, Hashimoto M, Ohni M, Toba K. Interrelationship between non-invasive measurements of atherosclerosis: flow-mediated dilation of brachial artery, carotid intima-media thickness and pulse wave velocity. Atherosclerosis. 2004;173(1):13–8.
  Article CAS PubMed Google Scholar
• Koivistoinen T, Virtanen M, Hutri-Kahonen N, Lehtimaki T, Jula A, Juonala M, et al. Arterial pulse wave velocity in relation to carotid intima-media thickness, brachial flow-mediated dilation and carotid artery distensibility: the Cardiovascular Risk in Young Finns Study and the Health 2000 Survey. Atherosclerosis. 2012;220(2):387–93.
  Article CAS PubMed Google Scholar
• Horvath T, Pinter A, Kollai M. Carotid artery stiffness is not related to endothelial function in young healthy subjects. Autonomic Neurosci Basic Clin. 2012;166(1-2):85–8.
  Article CAS Google Scholar
• Dubin R, Owens C, Gasper W, Ganz P, Johansen K. Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension. Hemodial Int Int Symp Home Hemodial. 2011;15(3):350–8.
  Article Google Scholar
• Cakar M, Bulucu F, Karaman M, Ay SA, Kurt O, Balta S, Demirkol S, Sarlak H, Akhan M, Altun B et al: Asymmetric Dimethylarginine and Augmentation Index in Newly Diagnosed Patients With Hypertension. Angiology 2013
• Wang KL, Cheng HM, Chuang SY, Spurgeon HA, Ting CT, Lakatta EG, et al. Central or peripheral systolic or pulse pressure: which best relates to target organs and future mortality? J Hypertens. 2009;27(3):461–7.
  Article PubMed Central CAS PubMed Google Scholar
• Gkaliagkousi E, Gavriilaki E, Nikolaidou B, Chatzopoulou F, Anyfanti P, Triantafyllou A, Petidis K, Zamboulis C, Douma S: Association Between Cardiotrophin 1 Levels and Central Blood Pressure in Untreated Patients With Essential Hypertension. American journal of hypertension 2014.
• Gkaliagkousi E, Doumas M, Gavriilaki E, Triantafyllou A, Vogiatzis K, Anyfanti P, et al. Elevated levels of MMP-9 in untreated patients with stage I essential hypertension. Clin Exp Hypertens. 2012;34(8):561–6.
  Article CAS PubMed Google Scholar
• Michelson G, Warntges S, Harazny J, Oehmer S, Delles C, Schmieder RE. Effect of nos inhibition on retinal arterial and capillary circulation in early arterial hypertension. Retina. 2006;26(4):437–44.
  Article PubMed Google Scholar
• Hemminki V, Laakso J, Kahonen M, Turjanmaa V, Uusitalo H, Lehtimaki T, et al. Plasma asymmetric dimethylarginine and retinal vessel diameters in middle-aged men. Metab Clin Exp. 2007;56(10):1305–10.
  Article CAS PubMed Google Scholar
• Tsioufis C, Dimitriadis K, Andrikou E, Thomopoulos C, Tsiachris D, Stefanadi E, et al. ADMA, C-reactive protein, and albuminuria in untreated essential hypertension: a cross-sectional study. Am J Kidney Dis Off J National Kidney Found. 2010;55(6):1050–9.
  Article CAS Google Scholar
• Rochette L, Lorin J, Zeller M, Guilland JC, Lorgis L, Cottin Y, et al. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets? Pharmacol Ther. 2013;140(3):239–57.
  Article CAS PubMed Google Scholar
• Shatanawi A, Romero MJ, Iddings JA, Chandra S, Umapathy NS, Verin AD, et al. Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway. Am J Physiol Cell Physiol. 2011;300(5):C1181–1192. A recent review with a detailed description of possible therapeutic targets of endothelial dysfunction in patients at increased cardiovascular risk.
  Article PubMed Central CAS PubMed Google Scholar
• Endtmann C, Ebrahimian T, Czech T, Arfa O, Laufs U, Fritz M, et al. Angiotensin II impairs endothelial progenitor cell number and function in vitro and in vivo: implications for vascular regeneration. Hypertension. 2011;58(3):394–403.
  Article CAS PubMed Google Scholar
• He HL, Liu L, Chen QH, Cai SX, Han JB, Hu SL, et al. MSCs modified with ACE2 restore endothelial function following LPS challenge by inhibiting the activation of RAS. J Cell Physiol. 2015;230(3):691–701.
  Article CAS PubMed Google Scholar
• Schlimmer N, Kratz M, Bohm M, Baumhakel M. Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis. Br J Pharmacol. 2011;163(4):804–14.
  Article PubMed Central CAS PubMed Google Scholar
• Yung LM, Wong WT, Tian XY, Leung FP, Yung LH, Chen ZY, et al. Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats. PLoS One. 2011;6(3):e17437.
  Article PubMed Central CAS PubMed Google Scholar
• Nemoto S, Kobayashi T, Taguchi K, Matsumoto T, Kamata K. Losartan improves aortic endothelium-dependent relaxation via proline-rich tyrosine kinase 2/Src/Akt pathway in type 2 diabetic Goto-Kakizaki rats. Am J Physiol Heart Circ Physiol. 2011;301(6):H2383–2394.
  Article CAS PubMed Google Scholar
• Tian S, Ge X, Wu K, Yang H, Liu Y. Ramipril protects the endothelium from high glucose-induced dysfunction through CaMKKbeta/AMPK and heme oxygenase-1 activation. J Pharmacol Exp Rapeutics. 2014;350(1):5–13.
  Article Google Scholar
• Toba H, Wang J, Ohigashi M, Kobara M, Nakata T. Telmisartan protects against vascular dysfunction with peroxisome proliferator-activated receptor-gamma activation in hypertensive 5/6 nephrectomized rats. Pharmacology. 2013;92(5-6):265–75.
  Article CAS PubMed Google Scholar
• Marampon F, Gravina GL, Scarsella L, Festuccia C, Lovat F, Ciccarelli C, et al. Angiotensin-converting-enzyme inhibition counteracts angiotensin II-mediated endothelial cell dysfunction by modulating the p38/SirT1 axis. J Hypertens. 2013;31(10):1972–83.
  Article CAS PubMed Google Scholar
• Siragusa M, Sessa WC. Telmisartan exerts pleiotropic effects in endothelial cells and promotes endothelial cell quiescence and survival. Arterioscler Thromb Vasc Biol. 2013;33(8):1852–60.
  Article CAS PubMed Google Scholar
• Mak IT, Landgraf KM, Chmielinska JJ, Weglicki WB. Angiotensin II promotes iron accumulation and depresses PGI(2) and NO synthesis in endothelial cells: effects of losartan and propranolol analogs. Can J Physiol Pharmacol. 2012;90(10):1413–8.
  Article PubMed Central CAS PubMed Google Scholar
• Georgescu A, Alexandru N, Andrei E, Titorencu I, Dragan E, Tarziu C, et al. Circulating microparticles and endothelial progenitor cells in atherosclerosis: pharmacological effects of irbesartan. J Thromb Haemost JTH. 2012;10(4):680–91.
  Article CAS PubMed Google Scholar
• Toyama T, Sato C, Koyama K, Kasama S, Murakami J, Yamashita E, et al. Olmesartan improves coronary flow reserve of hypertensive patients using coronary magnetic resonance imaging compared with amlodipine. Cardiology. 2012;122(4):230–6.
  Article CAS PubMed Google Scholar
• Cherney DZ, Scholey JW, Jiang S, Har R, Lai V, Sochett EB, et al. The effect of direct renin inhibition alone and in combination with ACE inhibition on endothelial function, arterial stiffness, and renal function in type 1 diabetes. Diabetes Care. 2012;35(11):2324–30.
  Article PubMed Central CAS PubMed Google Scholar
• Zankl AR, Ivandic B, Andrassy M, Volz HC, Krumsdorf U, Blessing E, et al. Telmisartan improves absolute walking distance and endothelial function in patients with peripheral artery disease. Clin Res cardiol Off J German Cardiac Soc. 2010;99(12):787–94.
  Article CAS Google Scholar
• Terashima M, Kaneda H, Nasu K, Matsuo H, Habara M, Ito T, et al. Protective effect of telmisartan against endothelial dysfunction after coronary drug-eluting stent implantation in hypertensive patients. J Am Coll Cardiol Intv. 2012;5(2):182–90.
  Article Google Scholar
• Suzuki R, Fukuda N, Katakawa M, Tsunemi A, Tahira Y, Matsumoto T, et al. Effects of an angiotensin II receptor blocker on the impaired function of endothelial progenitor cells in patients with essential hypertension. Am J Hypertens. 2014;27(5):695–701.
  Article CAS PubMed Google Scholar
• Cangiano E, Marchesini J, Campo G, Francolini G, Fortini C, Carra G, et al. ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes. Am J cardiovasc Drugs Drugs devices Other interv. 2011;11(3):189–98.
  Article CAS Google Scholar
• Shahin Y, Khan JA, Samuel N, Chetter I. Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials. Atherosclerosis. 2011;216(1):7–16.
  Article CAS PubMed Google Scholar
• Mason RP, Jacob RF, Corbalan JJ, Kaliszan R, Malinski T. Amlodipine increased endothelial nitric oxide and decreased nitroxidative stress disproportionately to blood pressure changes. Am J Hypertens. 2014;27(3):482–8.
  Article PubMed Central CAS PubMed Google Scholar
• He X, Zhang HL, Zhao M, Yang JL, Cheng G, Sun L, et al. Amlodipine ameliorates endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 2011;38(4):255–61.
  Article CAS PubMed Google Scholar
• Zhou MS, Tian R, Jaimes EA, Raij L. Combination therapy of amlodipine and atorvastatin has more beneficial vascular effects than monotherapy in salt-sensitive hypertension. Am J Hypertens. 2014;27(6):873–80.
  Article CAS PubMed Google Scholar
• Okamura T, Tawa M, Geddawy A, Shimosato T, Iwasaki H, Shintaku H, et al. Effects of atorvastatin, amlodipine, and their combination on vascular dysfunction in insulin-resistant rats. J Pharmacol Sci. 2014;124(1):76–85.
  Article CAS PubMed Google Scholar
• He Y, Si D, Yang C, Ni L, Li B, Ding M, et al. The effects of amlodipine and S(-)-amlodipine on vascular endothelial function in patients with hypertension. Am J Hypertens. 2014;27(1):27–31.
  Article CAS PubMed Google Scholar
• Bayar E, Ilhan G, Furat C, Atik C, Arslanoglu Y, Kuran C, et al. The effect of different beta-blockers on vascular graft nitric oxide levels: comparison of nebivolol versus metoprolol. Eur J Vascular Endovascular Surg Off J Eur Soc Vasc Surg. 2014;47(2):204–8.
  Article CAS Google Scholar
• Mason RP, Jacob RF, Corbalan JJ, Szczesny D, Matysiak K, Malinski T. The favorable kinetics and balance of nebivolol-stimulated nitric oxide and peroxynitrite release in human endothelial cells. BMC Pharmacol Toxicol. 2013;14:48.
  Article PubMed Central PubMed Google Scholar
• Doggen K, Fransen P, Lemmens K, De Keulenaer GW. Effects of nebivolol on vascular endothelial and myocardial function in diabetes mellitus. J Cardiovasc Pharmacol. 2011;58(1):56–64.
  Article CAS PubMed Google Scholar
• Wang Y, Zhang M, Liu Y, Chen M. The effect of nebivolol on asymmetric dimethylarginine system in spontaneously hypertension rats. Vasc Pharmacol. 2011;54(1-2):36–43.
  Article CAS Google Scholar
• Sorrentino SA, Doerries C, Manes C, Speer T, Dessy C, Lobysheva I, 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 beta1-blockade. J Am Coll Cardiol. 2011;57(5):601–11.
  Article CAS PubMed Google Scholar
• Zepeda RJ, Castillo R, Rodrigo R, Prieto JC, Aramburu I, Brugere S, et al. Effect of carvedilol and nebivolol on oxidative stress-related parameters and endothelial function in patients with essential hypertension. Basic Clin Pharmacol Toxicol. 2012;111(5):309–16.
  Article CAS PubMed Google Scholar
• Khan BV, Rahman ST, Haque T, Merchant N, Bhaheetharan S, Harris 3rd J, et al. Vascular effects of nebivolol added to hydrochlorothiazide in African Americans with hypertension and echocardiographic evidence of diastolic dysfunction: the NASAA study. J Cardiovasc Pharmacol Ther. 2012;17(3):291–7.
  Article CAS PubMed Google Scholar
• Sacco G, Evangelista S, Manzini S, Parlani M, Bigioni M. Combined antihypertensive and cardioprotective effects of nebivolol and hydrochlorothiazide in spontaneous hypertensive rats. Futur Cardiol. 2011;7(6):757–63.
  Article CAS Google Scholar
• Pasini AF, Garbin U, Stranieri C, Boccioletti V, Mozzini C, Manfro S, et al. Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients. Am J Hypertens. 2008;21(11):1251–7.
  Article CAS PubMed Google Scholar
• Momi S, Caracchini R, Falcinelli E, Evangelista S, Gresele P. Stimulation of platelet nitric oxide production by nebivolol prevents thrombosis. Arterioscler Thromb Vasc Biol. 2014;34(4):820–9.
  Article CAS PubMed Google Scholar
• Vitale C, Marazzi G, Iellamo F, Spoletini I, Dall’Armi V, Fini M, et al. Effects of nebivolol or irbesartan in combination with hydrochlorothiazide on vascular functions in newly-diagnosed hypertensive patients: the NINFE (Nebivololo, Irbesartan Nella Funzione Endoteliale) study. Int J Cardiol. 2012;155(2):279–84.
  Article PubMed Google Scholar
• Wolfrum S, Jensen KS, Liao JK. Endothelium-dependent effects of statins. Arterioscler Thromb Vasc Biol. 2003;23(5):729–36.
  Article CAS PubMed Google Scholar
• Reriani MK, Dunlay SM, Gupta B, West CP, Rihal CS, Lerman LO, et al. Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials. Eur J Cardiovascular Prev Rehabil Off J Eur Soc Cardiol Working Groups Epidemiol Prev Cardiac Rehabil Exerc Physiol. 2011;18(5):704–16.
  Google Scholar
• Wang Q, Yang M, Xu H, Yu J. Tetrahydrobiopterin improves endothelial function in cardiovascular disease: a systematic review. Evid-Based Complement Altern Med eCAM. 2014;2014:850312.
  Google Scholar
• Porkert M, Sher S, Reddy U, Cheema F, Niessner C, Kolm P, et al. Tetrahydrobiopterin: a novel antihypertensive therapy. J Hum Hypertens. 2008;22(6):401–7.
  Article CAS PubMed Google Scholar