L-精氨酸对高血压大鼠主动脉平滑肌细胞凋亡的影响

The Effects of L-arginine on Apoptosis of Aortic Smooth Muscle Cells in Renovascular Hypertensive Rats

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平滑肌细胞凋亡的影响。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):假手术对照组;高血压对照组(2K1C组);L-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;L-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,处死大鼠,用比色法测定血浆一氧化氮(NO)含量;分离胸主动脉检测胸主动脉平滑肌细胞凋亡(原位末端标记法)。结果与假手术组大鼠相比,2K1C组大鼠血压明显升高,胸主动脉平滑肌细胞凋亡指数升高,而血浆NO含量明显降低。应用L-精氨酸治疗则明显降低了肾动脉狭窄术后高血压大鼠的血压,升高了血浆NO含量,同时也使胸主动脉平滑肌细胞凋亡指数进一步增大。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-精氨酸治疗可刺激高血压血管平滑肌细胞凋亡增加。

Objective To investigate the effects of L-arginine on apoptosis of aortic smooth muscle cells 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） ：（1）the sham-operated control group ;（2）the 2K1C renohypertensive 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;（4）the 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 standard tail-cuff methods artery constriction. Indirect blood pressure was measured in conscious rats by the After treatment with both drugs for 8 weeks, the rats were killed, the plasma nitric oxide level was measured by colorimetric method, and the thoracic aorta was removed to determine apoptosis of aortic smooth muscle cell by using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method. Results Compared with the sham-operated control group, the untreated 2K1C renohypertensive rats exhibited an increase in blood pressure and apoptotic index of aortic smooth muscle cell, but a decrease in plasma nitric oxide level. L-arginine significantly inhibited the increase in blood pressure, but elevated the plasma nitric oxide level and the apoptotic index of aortic smooth muscle cell in 2K1C renovascular hypertensive rats; and these effects of L-arginine can be inhibited by L-NAME. Conclusion Long-term treatment with L-arginine can stimulate an increase in apoptosis of aortic smooth muscle cell in hypertensive rats.