L-精氨酸对肾性高血压大鼠心血管组织RAS的影响

The Effects of L-arginine on Renin-Angiotensin System in Cardiovascular Tissue of Rats with Renovascular Hypertension

目的探讨一氧化氮前体L-精氨酸对肾血管性高血压大鼠心血管组织局部肾素-血管紧张素系统(RAS)的影响。方法采用两肾一夹(2K1C)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):①假手术对照组;②高血压对照组;③L-精氨酸治疗组,于术后第5周开始给予L-精氨酸200 mg.kg-1.d-1;④L-NAME处理组,于术后第5周开始同时给予L-NAME 10 mg.kg-1.d-1及L-精氨酸200 mg.kg-1.d-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,分离心脏及主动脉用于检测组织血管紧张素Ⅱ含量(放射免疫法检测)和血管紧张素转换酶活性(分光光度计法检测)。结果与假手术对照组大鼠相比,未给药2K1C高血压大鼠血压明显升高,心脏及主动脉的血管紧张素Ⅱ(AngⅡ)含量增加和血管紧张素转换酶(ACE)活性增高。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高血压大鼠心脏及主动脉的AngⅡ含量和ACE活性。NOS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-精氨酸降压机制可能与抑制心血管组织局部RAS有关。

Objective To investigate the role of L-arginine on renin-angiotensin system（RAS） in cardiovascular tissue of rats with renovascular hypertension. Methods The renovascular hypertension model was induced in rats by two-kidney-one-clip（2K1C） method. All the rats were randomly divided into four groups （n= 10 per group）. ①the sham-operated control group;②the 2K1C renohypertension control group;③ the L-Arg group, the 2K1C rats were treated with L-arginine at a dose of 200mg · kg^-1 · d^-1 from 5th week after renal artery constriction; ④the L-NAME （Nitroarginine methyl ester） group, the 2KIC rats were treated with L-NAME （10 mg·kg^-1·d^-1） plus L-arginine （200mg·kg^-1·d^-1） from 5th week after renal artery constriction. Indirect blood pressure was measured in conscious rats hy the standard tail-cuff methods. After treatment with both drugs for 8 weeks, the rats were killed and the heart and aorta were removed to determine angiotensin 11 content by radioimmunoassay and angiotensin-converting enzyme activity by spectrophotometric method. Results Compared with the shamperated control group, the untreated 2K1C renohypertensive rats exhibited an increase in blood pressure, aortic angiotensin Ⅱ content and angiotensin-converting enzyme activity of the heart and aorta. L-arginine significantly inhibited the increase in blood pressure, aortic angiotensin Ⅱ content and angiotensin-converting enzyme activity of the heart and aorta in 2KIC renovascular hypertensive rats; and these effects of L-arginine could be inhibited by L-NAME. Conclusion Long-term treatment with L-arginine could lower blood pressure in renovascular hypertensive rats, which might be related to its inhibition on local tissue renin-angiotensin system.