Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure
Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure
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DOI：
10.1161/circulationaha.104.510248
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发表时间：
2005-05-31
期刊：
影响因子：
37.8
通讯作者：
Sunagawa, K
中科院分区：
文献类型：
--
作者：
Kishi, T;Hirooka, Y;Sunagawa, K
背景--在心力衰竭(HF)动物模型中，Rho-Kinase被认为在增强血管收缩中起重要作用。心力衰竭患者的特点是血管收缩增加，对反应性充血和运动的血管扩张反应减弱。本研究的目的是研究Rho-Kinase是否参与了服用Rho-Kinase抑制剂的人心力衰竭的外周循环异常。方法和结果：研究对象为心力衰竭患者(心力衰竭组，n=26)和年龄匹配的对照组(n=26)。在动脉内注入不同剂量的法舒地尔或硝普钠时，用应变式体积描记仪测量前臂血流量。心力衰竭组静息前臂血管阻力(FVR)明显高于对照组。法舒地尔引起的前臂血流量增加在心力衰竭组明显大于对照组。法舒地尔使心力衰竭组增加的FVR降低，接近对照组水平。相比之下，硝普钠诱发的FVR在两组之间具有可比性。在HF组，法舒地尔显著增强前臂动脉闭塞后反应性充血时受损的缺血性血管扩张，而对照组则无此作用。在对照组中，法舒地尔对苯肾上腺素诱发的FVR增加没有明显的增强作用。结论--这些结果表明Rho-Kinase参与了HF患者前臂FVR的增加和前臂血管扩张的受损。
Background - Rho-kinase is suggested to have an important role in enhanced vasoconstriction in animal models of heart failure (HF). Patients with HF are characterized by increased vasoconstriction and reduced vasodilator responses to reactive hyperemia and exercise. The aim of the present study was to examine whether Rho-kinase is involved in the peripheral circulation abnormalities of HF in humans with the Rho-kinase inhibitor fasudil.Methods and Results - Studies were performed in patients with HF (HF group, n = 26) and an age-matched control group (n = 26). Forearm blood flow was measured with a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil or sodium nitroprusside. Resting forearm vascular resistance (FVR) was significantly higher in the HF group than in the control group. The increase in forearm blood flow evoked by fasudil was significantly greater in the HF group than in the control group. The increased FVR was decreased by fasudil in the HF group toward the level of the control group. By contrast, FVR evoked by sodium nitroprusside was comparable between the 2 groups. Fasudil significantly augmented the impaired ischemic vasodilation during reactive hyperemia after arterial occlusion of the forearm in the HF group but not in the control group. Fasudil did not augment the increased FVR evoked by phenylephrine in the control group significantly.Conclusions - These results indicate that Rho-kinase is involved in increased FVR and impaired vasodilation of the forearm in patients with HF.