摘要
目的探讨一氧化氮前体L-精氨酸对肾血管性高血压大鼠主动脉肥厚及组织局部肾素-血管紧张素系统(RAS)的影响。方法采用两肾一夹型肾血管性高血压大鼠模型。所有大鼠被随机分为4组(每组10只):假手术对照组;高血压对照组;L-精氨酸治疗组,于术后第5周开始给予L-精氨酸200mg·kg-1·d-1;L-NAME处理组,于术后第5周开始同时给予L-NAME10mg·kg-1·d-1及L-精氨酸200mg·kg-1-1。采用标准尾套法间接检测清醒大鼠血压。给药8周后,大鼠处死,分离其胸主动脉以用于检测胸主动脉的血管紧张素Ⅱ含量(放射免疫法检测)、血管紧张素转化酶活性(分光光度计法检测)和胸主动脉中膜厚度及中膜截面积。结果与假手术组大鼠相比,未给药两肾一夹(2K1C)高血压大鼠血压明显升高,胸主动脉的血管紧张素Ⅱ含量增加和血管紧张素转化酶活性增高,主动脉中膜厚度及中膜截面积明显增大。应用L-精氨酸治疗则明显抑制了肾动脉狭窄术后大鼠血压的升高,降低了2K1C高血压大鼠胸主动脉的血管紧张素Ⅱ含量和血管紧张素转化酶活性,并减小了主动脉中膜厚度及中膜截面积。一氧化氮酶抑制剂L-NAME明显抑制了L-精氨酸的上述作用。结论长疗程L-精氨酸治疗可抑制肾性高血压大鼠主动脉肥厚的发生,其机制可能与抑制主动脉组织局部血管紧张素Ⅱ生成有关。
Abstract
OBJECTIVE To investigate the role of L-arginine on aortic hypertrophy and local tissue renin-angiotensin system in renovascular hypertensive rats.METHODS The renovascular hypertension model was induced in rats by two-kidney-one-clip method. All the rats were randomly divided into four groups (n=10 per group):the sham-operated control group;②the 2K1C renohypertensive control group;③the L-Arg group, the 2K1C rats were treated with L-arginine at a dose of 200 mg·kg-1·d-1 from 5th week after renal artery constriction;④the L-NAME group, the 2K1C rats were treated with L-NAME (10 mg·kg-1·d-1) plus L-arginine (200 mg·kg-1·d-1) from 5th week after renal artery constriction. Indirect blood pressure was measured in conscious rats by the standard tail-cuff methods. After treatment with both drugs for 8 weeks, the rats were killed and the thoracic aorta was removed to determine angiotensin Ⅱ content by radioimmunoassay, angiotensin-converting enzyme activity by spectrophotometric method, media thickness, and media cross-sectional area of thoracic aorta by a color image analysis system.RESULTS Compared with the sham-operated control group, the untreated 2K1C renohypertensive rats exhibited an increase in blood pressure, aortic angiotensin Ⅱ content, angiotensin-converting enzyme activity, media thickness, and media cross-sectional area of thoracic aorta. L-arginine significantly inhibited the increase in blood pressure, aortic angiotensin Ⅱ content, angiotensin-converting enzyme activity, media thickness, and media cross-sectional area of thoracic aorta in 2K1C renovascular hypertensive rats; and these effects of L-arginine were inhibited by L-NAME.CONCLUSION Long-term treatment with L-arginine can inhibit aortic hypertrophy in renovascular hypertensive rats, which may be related to its inhibition of tissue angiotensin Ⅱ generation.
关键词
高血压 /
主动脉 /
血管肥厚 /
血管紧张素Ⅱ /
血管紧张素转化酶 /
L-精氨酸
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Key words
hypertension /
aorta /
vascular hypertrophy /
angiotensin Ⅱ /
angiotensin-converting enzyme /
L-arginine
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余良主;魏劲波;化长林.
L-精氨酸对肾性高血压大鼠主动脉肥厚及组织局部RAS的影响[J]. 中国药学杂志, 2006, 41(23): 1781-1783
YU Ling-zhu;WEI Jin-o;HU Chng-lin.
Effects of L-arginine on Aortic Hypertrophy in Renovascular Hypertensive Rats [J]. Chinese Pharmaceutical Journal, 2006, 41(23): 1781-1783
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脚注
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