Comparison of Combination Therapy of Olmesartan plus Azelnidipine or Hydrochlorothiazide on Renal and Vascular Damage in SHR/NDmcr-cp Rats
Comparison of Combination Therapy of Olmesartan plus Azelnidipine or Hydrochlorothiazide on Renal and Vascular Damage in SHR/NDmcr-cp Rats
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DOI：
10.1159/000323535
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发表时间：
2011-01-01
影响因子：
2.8
通讯作者：
Kashihara, Naoki
中科院分区：
文献类型：
--
作者：
Nagasu, Hajime;Satoh, Minoru;Kashihara, Naoki
背景资料：尽管慢性肾脏病患者的推荐目标血压为< 130/80 mm Hg，但仅用血管紧张素受体阻滞剂治疗难以达到这一目标。建议添加钙通道阻滞剂或利尿剂作为二线药物;然而，哪种组合对靶器官保护最有益仍不清楚。研究方法：SHR/NDmcr-cp大鼠给予无药物（对照）或低剂量奥美沙坦2周，然后给予增加剂量的奥美沙坦、阿折地平或氢氯噻嗪3周。我们评估了肾脏和主动脉的氧化应激和内皮功能。结果：治疗组大鼠尿蛋白排泄量明显低于对照组。在对照大鼠的肾小球和主动脉中观察到由NAD（P）H氧化酶激活引起的氧化应激，并且在奥美沙坦/阿折地平（Olm/Azl）组中被显著抑制。然而，奥美沙坦和氢氯噻嗪（Olm/HCTZ）联合治疗未能抑制氧化应激。Olm/Azl组维持肾小球中的内皮表面层并保护主动脉中的内皮功能。结论：在代谢综合征的动物模型中，Olm/Azl的组合在预防肾小球和血管损伤方面上级Olm/HCTZ的组合。版权所有（C）2011 S. Karger AG，巴塞尔
Background: Although the recommended target blood pressure for patients with chronic kidney disease is < 130/80 mm Hg, this is difficult to achieve by treatment with an angiotensin receptor blocker alone. Addition of either a calcium channel blocker or a diuretic is suggested as second-line medication; however, which combination is most beneficial for target-organ protection remains unknown. Methods: SHR/NDmcr-cp rats were administered no medications ( control) or low-dose olmesartan for 2 weeks and then either olmesartan at an increased dose, azelnidipine, or the hydrochlorothiazide for 3 weeks. We assessed oxidative stress in the kidney and aorta, and endothelial function. Results: Urinary protein excretion was lower in all treated rats than in control rats. Oxidative stress caused by activation of NAD(P)H oxidase was observed in the glomeruli and aorta of control rats and was significantly suppressed in the olmesartan/azelnidipine (Olm/Azl) groups. Combination therapy with olmesartan and hydrochlorothiazide (Olm/HCTZ) however failed to suppress oxidative stress. The Olm/Azl groups maintained the endothelial surface layer in the glomeruli and protected endothelial function in the aorta. Conclusion: In an animal model of metabolic syndrome, a combination of Olm/Azl is superior to a combination of Olm/HCTZ in terms of prevention of glomerular and vascular injuries. Copyright (C) 2011 S. Karger AG, Basel