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血管紧张素转换酶抑制剂对两肾一夹型 Goldblatt 高血压大鼠和假手术大鼠阻力动脉结构及内皮依赖性舒张功能的影响

Effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in two-kidney, one-clip Goldblatt hypertensive and sham-operated rats.

作者信息

Bennett M A, Thurston H

机构信息

Department of Medicine and Therapeutics, Leicester Royal Infirmary, U.K.

出版信息

Clin Sci (Lond). 1996 Jan;90(1):21-9. doi: 10.1042/cs0900021.

Abstract
  1. This study was designed to examine the effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in Goldblatt two-kidney, one-clip hypertensive rats. Four weeks after clipping, hypertensive and sham rats were treated with either perindopril (1 mg day-1 kg-1) or quinapril (3 or 30 mg day-1 kg-1). After 6 weeks mesenteric resistance arteries were mounted in a myograph for measurements of vascular structure. The endothelium-dependent relaxation response to acetylcholine and bradykinin and the response to the nitric oxide donor sodium nitroprusside were recorded. 2. All treatment regimes lowered the blood pressure and reversed both cardiac and resistance artery hypertrophy. Two-kidney, one-clip rats treated with quinapril showed a dose-dependent reduction in media cross-sectional area and media to lumen ratio. 3. Hypertension of 10 weeks' duration was associated with an impaired endothelium-dependent relaxation response to acetylcholine and bradykinin. Treatment with perindopril and either dose of quinapril prevented the development of impaired endothelium-dependent relaxation but had no effect on the response to sodium nitroprusside. Treatment had no effect on endothelium-dependent relaxation in sham rats. 4. Angiotensin-converting enzyme inhibitor treatment is effective in normalizing blood pressure and cardiovascular structural changes. Angiotensin-converting enzyme inhibitor treatment prevented the development of impaired endothelium-dependent relaxation to both acetylcholine and bradykinin. The ability of angiotensin-converting enzyme inhibitors to reverse cardiovascular structural changes and prevent the development of abnormal endothelium-dependent relaxation may contribute to the overall effect of this type of antihypertensive drug.
摘要
  1. 本研究旨在探讨血管紧张素转换酶抑制剂对Goldblatt二肾一夹高血压大鼠阻力动脉结构及内皮依赖性舒张功能的影响。夹闭4周后,将高血压大鼠和假手术大鼠分别用培哚普利(1毫克/天·千克-1)或喹那普利(3或30毫克/天·千克-1)进行治疗。6周后,将肠系膜阻力动脉安装在肌动描记器上以测量血管结构。记录对乙酰胆碱和缓激肽的内皮依赖性舒张反应以及对一氧化氮供体硝普钠的反应。2. 所有治疗方案均降低了血压,并逆转了心脏和阻力动脉肥大。用喹那普利治疗的二肾一夹大鼠的中膜横截面积和中膜与管腔比值呈剂量依赖性降低。3. 持续10周的高血压与对乙酰胆碱和缓激肽的内皮依赖性舒张反应受损有关。用培哚普利和任一剂量的喹那普利治疗可防止内皮依赖性舒张功能受损的发生,但对硝普钠的反应无影响。治疗对假手术大鼠的内皮依赖性舒张功能无影响。4. 血管紧张素转换酶抑制剂治疗在使血压和心血管结构变化正常化方面有效。血管紧张素转换酶抑制剂治疗可防止对乙酰胆碱和缓激肽的内皮依赖性舒张功能受损的发生。血管紧张素转换酶抑制剂逆转心血管结构变化和防止异常内皮依赖性舒张功能发展的能力可能有助于这类抗高血压药物的总体疗效。

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