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首页> 外文期刊>Life sciences >Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.
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Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.

机译：新型V型磷酸二酯酶抑制剂DA-8159的慢性治疗可减轻易中风的自发性高血压大鼠的内皮功能障碍。

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This study examined the effects of chronic treatment of a new phosphodiesterase type 5 inhibitor, DA-8159, on endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHR-SP). Six-week-old male SHR-SP were divided into 4 groups; vehicle control, DA-8159 1, 3, and 10 mg/kg/day. During a 32-week experimental period, the animals were administered DA-8159 orally and fed a 4% NaCl-loaded diet. The systolic blood pressure was measured every two weeks throughout the experimental period using the tail-cuff method. At the end of experiments, the vascular function (acetylcholine-induced vasodilation) in the endothelium-intact aortic rings was investigated. In addition, the mortality, the left ventricular hypertrophy index, the plasma parameters and the incidence of a cerebral infarction were assessed. In the DA-8159 treated-rats, the vascular reactivity improved significantly in a dose-dependent manner. Although DA-8159 did not alter the elevation of the systolic blood pressure directly, the 3 and 10 mg/kg/day DA-8159 treatment delayed the early death caused by stroke. DA-8159 significantly reduced the left ventricular heart weight/body weight ratio compared with the vehicle control group. Furthermore, the DA-8159 treatment significantly increased the plasma nitric oxide, cGMP, and the total antioxidative status. The DA-8159 treatment also reduced the occurrence of stroke-associated cerebral damage. These results indicate that DA-8159 can ameliorate an endothelial dysfunction-related vascular injury. Therefore, pharmacological intervention aimed at attenuating an endothelial dysfunction is important and might be useful in both preventing and treating endothelial dysfunction-related complications.
机译：这项研究检查了新型5型磷酸二酯酶抑制剂DA-8159的慢性治疗对易发中风自发性高血压大鼠（SHR-SP）内皮功能的影响。六周大的男性SHR-SP分为4组;第二组为男性。媒介物控制，DA-8159 1、3和10 mg / kg /天。在32周的实验期内，给动物口服DA-8159并喂食4％NaCl饮食。在整个实验期间，使用尾袖套法每两周测量一次收缩压。在实验结束时，研究了内皮完整的主动脉环中的血管功能（乙酰胆碱诱导的血管舒张）。此外，还评估了死亡率，左心室肥厚指数，血浆参数和脑梗死的发生率。在DA-8159处理的大鼠中，血管反应性以剂量依赖性方式显着改善。尽管DA-8159并没有直接改变收缩压的升高，但是每天3和10 mg / kg / day的DA-8159治疗延迟了中风引起的早期死亡。与媒介物对照组相比，DA-8159显着降低了左心室心脏重量/体重比。此外，DA-8159处理显着增加了血浆一氧化氮，cGMP和总抗氧化状态。 DA-8159治疗还减少了中风相关性脑损伤的发生。这些结果表明DA-8159可以改善内皮功能障碍相关的血管损伤。因此，旨在减轻内皮功能障碍的药理学干预很重要，并且在预防和治疗与内皮功能障碍有关的并发症中可能有用。

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