Gouvea Sonia A, Bissoli Nazaré S, Moysés Margareth R, Cicilini Maria A, Pires José G P, Abreu Glaucia R
Department of Physiological Sciences, Biomedical Center, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil.
Clin Exp Hypertens. 2004 Aug;26(6):569-79. doi: 10.1081/ceh-200031837.
The renin-angiotensin system plays a role in the pathophysiology of renovascular hypertension. In addition, some studies have demonstrated a beneficial effect of L-arginine (L-Arg), the precursor of nitric oxide (NO), in this model of hypertension. This study was designed to investigate the effects of L-Arg on cardiovascular parameters and on the activity of the angiotensin-converting enzyme (ACE), after 14 days of renovascular hypertension. The experiments were performed on conscious male Wistar rats. Two-kidney, one-clip renovascular hypertension (2KIC) was initiated in rats by clipping the left renal artery during 14 days, while control rats were sham-operated. One group was submitted to a similar procedure and treated with L-Arg (10 mg/ml; average intake of 300mg/day) from the 7th to the 14th day after surgery, whereas the respective control group received water instead. At the end of the treatment period, the mean arterial pressure (MAP) was measured in conscious animals. The rats were sacrificed and the ACE activity was assayed in heart and kidneys, using Hip-His-Leu as substrate. In a separate group, the heart was removed, the left ventricle (LV) was weighed and the LV/body weight ratios (LV/BW) were determined. We observed significant differences in MAP between the L-Arg-treated and untreated groups (129 +/- 7 vs. 168 +/- 6 mmHg; P< 0.01). The cardiac hypertrophy described for this model of hypertension was attenuated in the 2K1C-L-Arg-treated group (14th day, wet LV/BW: 2K1C-L-Arg = 1.88 +/- 0.1; 2K1C = 2.20 +/- 0.1 mg/g; P < 0.05). L-Arg administration caused an important decrease in cardiac ACE activity (2K1C-L-Arg: 118 +/- 15; 2K1C: 266 +/- 34 micromol/min/mg; P < 0.01). L-Arg also decreased the ACE activity in the clipped kidney by 47% (P < 0.01), but not in the nonclipped kidney. These data suggest that increased NO formation and reduced angiotensin II formation are involved in the anthihypertensive effect of orally administered L-arginine.
肾素-血管紧张素系统在肾血管性高血压的病理生理过程中发挥作用。此外，一些研究已证明一氧化氮（NO）的前体L-精氨酸（L-Arg）在该高血压模型中具有有益作用。本研究旨在探讨肾血管性高血压14天后L-Arg对心血管参数及血管紧张素转换酶（ACE）活性的影响。实验在清醒的雄性Wistar大鼠身上进行。通过在14天内夹闭左肾动脉在大鼠中引发两肾一夹肾血管性高血压（2K1C），而对照大鼠进行假手术。一组接受类似手术，并在术后第7天至第14天用L-Arg（10mg/ml；平均摄入量为300mg/天）治疗，而相应的对照组给予水。在治疗期结束时，测量清醒动物的平均动脉压（MAP）。处死大鼠并以Hip-His-Leu为底物测定心脏和肾脏中的ACE活性。在另一组中，取出心脏，称量左心室（LV）重量并确定LV/体重比（LV/BW）。我们观察到L-Arg治疗组和未治疗组之间的MAP存在显著差异（129±7 vs. 168±6 mmHg；P<0.01）。在2K1C-L-Arg治疗组中，该高血压模型中描述的心脏肥大得到减轻（第14天，湿LV/BW：2K1C-L-Arg = 1.88±0.1；2K1C = 2.20±0.1mg/g；P<0.05）。给予L-Arg导致心脏ACE活性显著降低（2K1C-L-Arg：118±15；2K1C：266±34μmol/min/mg；P<0.01）。L-Arg还使夹闭肾脏中的ACE活性降低47%（P<0.01），但未夹闭的肾脏中未降低。这些数据表明，口服L-精氨酸的降压作用涉及NO生成增加和血管紧张素II生成减少。
