Nebivolol and metoprolol: long-term effects on inflammation and oxidative stress in essential hypertension

被引:35
作者
Serg, Martin [1 ,2 ]
Kampus, Priit [1 ,2 ,3 ]
Kals, Jaak [2 ,4 ]
Zagura, Maksim [1 ,2 ]
Zilmer, Mihkel [2 ]
Zilmer, Kersti [2 ]
Kullisaar, Tiiu [2 ]
Eha, Jaan [1 ,3 ]
机构
[1] Univ Tartu, Dept Cardiol, EE-51014 Tartu, Estonia
[2] Univ Tartu, Dept Biochem, Ctr Excellence Translat Med, EE-51014 Tartu, Estonia
[3] Tartu Univ Hosp, Heart Clin, Tartu, Estonia
[4] Tartu Univ Hosp, Dept Vasc Surg, Tartu, Estonia
关键词
Adrenergic beta-antagonists; isoprostanes; oxidized low density lipoprotein; cell adhesion molecules; LOW-DENSITY-LIPOPROTEIN; CENTRAL AORTIC PRESSURE; INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; NITRIC-OXIDE; ENDOTHELIAL FUNCTION; ARTERIAL STIFFNESS; LIPID-PEROXIDATION; BLOOD-PRESSURE; DISEASE;
D O I
10.3109/00365513.2012.691991
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p < 0.01 and for both drugs), but only nebivolol reduced 8-isoprostanes (p = 0.01). In the metoprolol group, change in oxLDL levels correlated with change in systolic blood pressure (r = 0.45; p < 0.01) and pulse pressure (r = 0.47; p < 0.01). Both metoprolol and nebivolol reduced ICAM-1 (p < 0.01). There was no change in IL-6, hsCRP, fibrinogen, or ADMA levels in either group. These data suggest that in long-term antihypertensive treatment both the cardioselective beta blocker metoprolol succinate and the vasodilating beta blocker nebivolol have inflammation-related effects but only nebivolol has a favourable blood pressure-independent effect on oxidative stress.
引用
收藏
页码:427 / 432
页数:6
相关论文
共 34 条
[1]   Guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health [J].
Agostoni, Carlo ;
Bresson, Jean-Louis ;
Fairweather-Tait, Susan ;
Flynn, Albert ;
Golly, Ines ;
Korhonen, Hannu ;
Lagiou, Pagona ;
Lovik, Martinus ;
Marchelli, Rosangela ;
Martin, Ambroise ;
Moseley, Bevan ;
Neuhauser-Berthold, Monika ;
Przyrembel, Hildegard ;
Salminen, Seppo ;
Sanz, Yolanda ;
Strain, Sean ;
Strobel, Stephan ;
Tetens, Inge ;
Tome, Daniel ;
van Loveren, Hendrik ;
Verhagen, Hans .
EFSA JOURNAL, 2011, 9 (12)
[2]   Comparative effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients [J].
Celik, T ;
Iyisoy, A ;
Kursaklioglu, H ;
Kardesoglu, E ;
Kilic, S ;
Turhan, H ;
Yilmaz, MI ;
Ozcan, O ;
Yaman, H ;
Isik, E ;
Fici, F .
JOURNAL OF HYPERTENSION, 2006, 24 (03) :591-596
[3]   Nebivolol and its 4-keto derivative increase nitric oxide in endothelial cells by reducing its oxidative inactivation [J].
Cominacini, L ;
Pasini, AF ;
Garbin, U ;
Nava, C ;
Davoli, A ;
Criscuoli, M ;
Crea, A ;
Sawamura, T ;
Lo Cascio, V .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2003, 42 (10) :1838-1844
[4]   C-reactive protein and intercellular adhesion molecule-1 are stronger predictors of oxidant stress than blood pressure in established hypertension [J].
Cottone, Santina ;
Mule, Giuseppe ;
Nardi, Emilio ;
Vadala, Anna ;
Lorito, Maria C. ;
Guarneri, Marco ;
Arsena, Rosalia ;
Palermo, Alessandro ;
Cerasola, Giovanni .
JOURNAL OF HYPERTENSION, 2007, 25 (02) :423-428
[5]   Candesartan effect on inflammation in hypertension [J].
Derosa, Giuseppe ;
Maffioli, Pamela ;
Salvadeo, Sibilla A. T. ;
Ferrari, Ilaria ;
Gravina, Alessia ;
Mereu, Roberto ;
Palumbo, Ilaria ;
D'Angelo, Angela ;
Cicero, Arrigo F. G. .
HYPERTENSION RESEARCH, 2010, 33 (03) :209-213
[6]   Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes [J].
Ehara, S ;
Ueda, M ;
Naruko, T ;
Haze, K ;
Itoh, A ;
Otsuka, M ;
Komatsu, R ;
Matsuo, T ;
Itabe, H ;
Takano, T ;
Tsukamoto, Y ;
Yoshiyama, M ;
Takeuchi, K ;
Yoshikawa, J ;
Becker, AE .
CIRCULATION, 2001, 103 (15) :1955-1960
[7]   Effect of DL-nebivolol, its enantiomers and metabolites on the intracellular production of superoxide and nitric oxide in human endothelial cells [J].
Evangelista, Stefano ;
Garbin, Ulisse ;
Fratta Pasini, Anna ;
Stranieri, Chiara ;
Boccioletti, Veronica ;
Cominacini, Luciano .
PHARMACOLOGICAL RESEARCH, 2007, 55 (04) :303-309
[8]   Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease [J].
Heitzer, T ;
Schlinzig, T ;
Krohn, K ;
Meinertz, T ;
Münzel, T .
CIRCULATION, 2001, 104 (22) :2673-2678
[9]   Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis [J].
Kals, Jaak ;
Kampus, Priit ;
Kals, Mart ;
Pulges, Andres ;
Teesalu, Rein ;
Zilmer, Kersti ;
Kullisaar, Tiiu ;
Salum, Tiit ;
Eha, Jaan ;
Zilmer, Mihkel .
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION, 2008, 68 (07) :594-601
[10]   Augmentation index and carotid intima-media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein [J].
Kampus, Priit ;
Kals, Jaak ;
Ristimae, Tiina ;
Muda, Piibe ;
Ulst, Kai ;
Zilmer, Kersti ;
Salonen, Riitta M. ;
Tuomainen, Tomi-Pekka ;
Teesalu, Rein ;
Zilmer, Mihkel .
JOURNAL OF HYPERTENSION, 2007, 25 (04) :819-825