Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats.
Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats.
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DOI：
10.1371/journal.pone.0039162
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kim-Mitsuyama S
中科院分区：
文献类型：
--
作者：
Yamamoto E;Kataoka K;Dong YF;Koibuchi N;Toyama K;Sueta D;Katayama T;Yasuda O;Ogawa H;Kim-Mitsuyama S
血管紧张素受体阻滞剂（ARB）与钙通道阻滞剂（CCB）或利尿剂的联合治疗被推荐用于治疗高血压。然而，这两种联合疗法之间的差异尚不清楚。目前的工作旨在研究两种联合疗法在血管保护方面可能存在的差异。将盐负荷性脑卒中易发性高血压大鼠（SHRSP）分为6组，口服（1）赋形剂，（2）奥美沙坦，ARB，（3）阿折地平，CCB，（4）氢氯噻嗪，利尿剂，（5）奥美沙坦联合阿折地平，或（6）奥美沙坦联合氢氯噻嗪。奥美沙坦联合阿折地平或氢氯噻嗪比单独使用任一药物更能改善 SHRSP 中的血管内皮功能障碍和重塑。然而，尽管两种治疗方法之间的降压效果相当，但阿折地平在负载盐的 SHRSP 中比氢氯噻嗪更大程度地增强了奥美沙坦对血管内皮功能障碍和重塑的改善作用。与氢氯噻嗪相比，阿折地平对奥美沙坦诱导的血管保护作用的增强与血管烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶激活、超氧化物、丝裂原激活蛋白激酶激活的更大改善以及Akt/内皮一氧化氮合酶（eNOS）途径的更大激活相关。这些结果提供了第一个证据，证明与利尿剂相比，CCB 可以增强 ARB 对盐敏感性高血压的血管保护作用，并提供了新的原理来解释 ARB 和 CCB 联合治疗的益处。
The combination therapy of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB) or with a diuretic is favorably recommended for the treatment of hypertension. However, the difference between these two combination therapies is unclear. The present work was undertaken to examine the possible difference between the two combination therapies in vascular protection. Salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 6 groups, and they were orally administered (1) vehicle, (2) olmesartan, an ARB, (3) azelnidipine, a CCB, (4) hydrochlorothiazide, a diuretic, (5) olmesartan combined with azelnidipine, or (6) olmesartan combined with hydrochlorothiazide. Olmesartan combined with either azelnidipine or hydrochlorothiazide ameliorated vascular endothelial dysfunction and remodeling in SHRSP more than did monotherapy with either agent. However, despite a comparable blood pressure lowering effect between the two treatments, azelnidipine enhanced the amelioration of vascular endothelial dysfunction and remodeling by olmesartan to a greater extent than did hydrochlorothiazide in salt-loaded SHRSP. The increased enhancement by azelnidipine of olmesartan-induced vascular protection than by hydrochlorothiazide was associated with a greater amelioration of vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, superoxide, mitogen-activated protein kinase activation, and with a greater activation of the Akt/endothelial nitric oxide synthase (eNOS) pathway. These results provided the first evidence that a CCB potentiates the vascular protective effects of an ARB in salt-sensitive hypertension, compared with a diuretic, and provided a novel rationale explaining the benefit of the combination therapy with an ARB and a CCB.
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影响因子：
37.8
作者：
Förstermann, U;Münzel, T
通讯作者：
Münzel, T
影响因子：
168.9
作者：
Morimoto, A;Uzu, T;Kimura, G
通讯作者：
Kimura, G
影响因子：
158.5
作者：
Jamerson, Kenneth;Weber, Michael A.;Velazquez, Eric J.
通讯作者：
Velazquez, Eric J.
影响因子：
8.3
作者：
Nakamura, Taishi;Yamamoto, Eiichiro;Kim-Mitsuyama, Shokei
通讯作者：
Kim-Mitsuyama, Shokei
DOI：
10.1161/01.atv.0000149143.04821.eb
发表时间：
2005-02-01
影响因子：
8.7
作者：
Mueller, CFH;Laude, K;Harrison, DG
通讯作者：
Harrison, DG