Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice.
Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice.
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DOI：
10.1371/journal.pone.0082082
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nishiyama A
中科院分区：
文献类型：
--
作者：
Rafiq K;Sherajee SJ;Hitomi H;Nakano D;Kobori H;Ohmori K;Mori H;Kobara H;Masaki T;Kohno M;Nishiyama A
最近的临床试验表明，肾素-血管紧张素系统抑制剂和钙通道阻滞剂（CCBs）联合治疗对心血管高危高血压患者的心血管和肾脏事件有有益的影响。在本研究中，我们假设CCB增强了血管紧张素II型1受体阻滞剂（ARB）对糖尿病脑血管肾损伤的保护作用。饮用盐碱的2型糖尿病KK-Ay小鼠出现高血压，并表现出认知功能受损、血脑屏障（BBB）破坏、蛋白尿、肾小球硬化和足细胞损伤。这些脑和肾损伤与NADPH氧化酶成分基因表达增加、NADPH氧化酶活性增加、脑和肾组织氧化应激以及全身氧化应激有关。用ARB治疗，奥美沙坦（10 mg/kg/天）降低了喝盐的KK-Ay小鼠的血压，减轻了认知能力下降、血脑屏障破坏、肾小球损伤和蛋白尿，这些与NADPH氧化酶活性降低、脑和肾脏组织氧化应激以及全身氧化应激有关。此外，阿泽尼地平的抑制剂量（3mg /kg/天）夸大了奥美沙坦的这些有益作用。这些数据支持了CCB通过抑制2型糖尿病患者NADPH氧化酶依赖的氧化应激而增强arb相关的脑血管肾保护作用的假设。
Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-Ay mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) reduced blood pressure in saline-drinking KK-Ay mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes.
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影响因子：
19.6
作者：
Ninomiya, T;Kiyohara, Y;Iida, M
通讯作者：
Iida, M
影响因子：
3.6
作者：
Li, JM;Iwai, M;Horiuchi, M
通讯作者：
Horiuchi, M
影响因子：
2.9
作者：
Autan, Sezen Milli;Kaya, Mehmet;Ahishali, Bulent
通讯作者：
Ahishali, Bulent
影响因子：
158.5
作者：
Jamerson, Kenneth;Weber, Michael A.;Velazquez, Eric J.
通讯作者：
Velazquez, Eric J.
DOI：
10.1073/pnas.1332809100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Liu, RL;Liu, IY;Baudry, M
通讯作者：
Baudry, M