Yoo Sae Mi, Choi Sung Hyun, Jung Monica Dha Yea, Lim Sung Cil, Baek Sang Hong
1] Laboratory of Cardiovascular Regeneration, Division of Cardiovascular Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea [2] Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Biochemistry, University of Rochester, Rochester, NY, USA.
Hypertens Res. 2015 Feb;38(2):106-15. doi: 10.1038/hr.2014.151. Epub 2014 Oct 16.
Reactive oxygen species (ROS) and antioxidant enzymes are required to maintain homeostasis. The loss of this balance can cause excessive ROS production and damage to the cardiovascular tissues. Angiotensin II receptor blockers (ARBs) and β-blockers with antioxidant effects may inhibit ROS in the cardiovascular system. In this study, we directly compared the effects of ARBs and β-blockers with antioxidant properties on cardiovascular protection and the regulation of endothelial progenitor cell (EPC) numbers in the setting of oxidative stress in hypertensive rats. To compare the effects of the drugs, animals were divided into the following groups: Wistar-Kyoto rats (WKY), untreated spontaneously hypertensive rats (SHR) and SHR treated with tempol (TEMP, 5 mg kg(-1) per day), trichlorothiazide (TCTZ, 1.6 mg kg(-1) per day), atenolol (25 mg kg(-1) per day), nebivolol (NEBL, 5 mg kg(-1) per day), carvedilol (CVDL, 30 mg kg(-1) per day) or telmisartan (TERT, 5 mg kg(-1) per day). Following 2 weeks of treatment, blood pressures (BPs) and aortic wall thicknesses were similarly reduced in each antihypertensive drug-treated group. Superoxide anion and malondialdehyde levels were significantly reduced following treatment with NEBL, CVDL and TERT. Additionally, the expression levels of NADPH oxidase subunits were also reduced in the TERT-, CVDL- and NEBL-treated groups. Furthermore, these drugs improved both EPC numbers and the expression levels of peroxiredoxin 2 (Prdx2), an antioxidant enzyme, in the heart and kidneys but not the aorta. Cardiac Prdx2 expression, in particular, was markedly improved by TERT, NEBL and CVDL treatment, and renal Prdx2 expression was enhanced by TEMP. Our data indicate that short-term treatment with TERT may have more beneficial effects on cardiovascular protection, EPC number improvements and Prdx2 expression compared with CVDL and NEBL. In conclusion, TERT may positively modulate the balance between oxidative stress and antioxidant properties and demonstrate capabilities beyond its BP-lowering effects.
活性氧（ROS）和抗氧化酶对于维持体内平衡是必需的。这种平衡的丧失会导致ROS过度产生并损害心血管组织。具有抗氧化作用的血管紧张素II受体阻滞剂（ARB）和β受体阻滞剂可能会抑制心血管系统中的ROS。在本研究中，我们直接比较了具有抗氧化特性的ARB和β受体阻滞剂在高血压大鼠氧化应激情况下对心血管保护以及内皮祖细胞（EPC）数量调节的影响。为了比较药物的效果，将动物分为以下几组：Wistar-Kyoto大鼠（WKY）、未经治疗的自发性高血压大鼠（SHR）以及用替莫泊尔（TEMP，每天5 mg kg⁻¹）、三氯噻嗪（TCTZ，每天1.6 mg kg⁻¹）、阿替洛尔（每天25 mg kg⁻¹）、奈必洛尔（NEBL，每天5 mg kg⁻¹）、卡维地洛（CVDL，每天30 mg kg⁻¹）或替米沙坦（TERT，每天5 mg kg⁻¹）治疗的SHR。治疗2周后，各降压药物治疗组的血压（BP）和主动脉壁厚度均有相似程度的降低。用NEBL、CVDL和TERT治疗后，超氧阴离子和丙二醛水平显著降低。此外，在TERT、CVDL和NEBL治疗组中，NADPH氧化酶亚基的表达水平也降低了。此外，这些药物改善了心脏和肾脏中EPC的数量以及抗氧化酶过氧化物酶2（Prdx2）的表达水平，但对主动脉没有影响。特别是，TERT、NEBL和CVDL治疗显著改善了心脏Prdx2的表达，TEMP增强了肾脏Prdx2的表达。我们的数据表明，与CVDL和NEBL相比，短期使用TERT可能对心血管保护、EPC数量改善和Prdx2表达具有更有益的作用。总之，TERT可能积极调节氧化应激和抗氧化特性之间的平衡，并展现出超出其降压作用的能力。
