Department of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, Japan.
Kidney Blood Press Res. 2011;34(2):87-96. doi: 10.1159/000323535. Epub 2011 Jan 27.
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.
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.
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.
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.
尽管建议慢性肾脏病患者的目标血压<130/80mmHg，但仅用血管紧张素受体阻滞剂治疗很难达到这一目标。建议在血管紧张素受体阻滞剂的基础上加用钙通道阻滞剂或利尿剂作为二线药物；然而，哪种联合用药对靶器官保护最有益仍不清楚。
SHR/NDmcr-cp 大鼠给予无药物治疗（对照组）或低剂量奥美沙坦治疗 2 周，然后给予奥美沙坦增加剂量、阿折地平或氢氯噻嗪治疗 3 周。我们评估了肾脏和主动脉的氧化应激和内皮功能。
所有治疗组大鼠的尿蛋白排泄均低于对照组。对照组大鼠的肾小球和主动脉中观察到 NAD(P)H 氧化酶激活引起的氧化应激，奥美沙坦/阿折地平（Olm/Azl）组的氧化应激明显受到抑制。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 组在肾小球中维持内皮表面层，并保护主动脉内皮功能。
在代谢综合征动物模型中，奥美沙坦/阿折地平联合治疗在预防肾小球和血管损伤方面优于奥美沙坦/氢氯噻嗪联合治疗。
