Ninahuaman M F M L, Souccar C, Lapa A J, Lima-Landman M T R
Universidade Federal de São Paulo, Department of Pharmacology, Natural Products Section, 04044-020 São Paulo, SP, Brazil.
Phytomedicine. 2007 May;14(5):321-7. doi: 10.1016/j.phymed.2006.12.010. Epub 2007 Apr 12.
To evaluate the effect of the standardized aqueous extract (AE) of Cecropia glaziovii Sneth on the plasma angiotensin I converting enzyme (ACE-EC 3.4.15.1) activity, rats were treated with a single dose of AE (1 g/kg, p.o.) or repeatedly (0.5 g/kg/bid, p.o.) for 60 days. Captopril (50 mg/kg, p.o.) was used as positive control on the same animals. The effects on the blood pressure were recorded directly from the femoral artery (single dose), or indirectly by the tail cuff method (repeated doses) in conscious rats. The plasma ACE activity was determined spectrofluorimetrically using Hypuril-Hystidine-Leucine as substrate. The arterial blood pressure, heart rate and plasma ACE activity were not significantly modified within 24 h after a single dose administration of AE. Comparatively, blood pressure in captopril treated rats was reduced by 7-16% and heart rate was increased by 10-20% from 30 min to 24 h after drug administration. ACE activity after captopril presented a dual response: an immediate inhibition peaking at 30 min and a slow reversal to 32% up-regulation after 24 h. To correlate the drug effects upon repeated administration of either compound, normotensive rats were separated in three groups: animals with high ACE (48.8+/-2.6 nmol/min/ml), intermediate ACE (39.4+/-1.4 nmol/min/ml) and low ACE (23.5+/-0.6 nmol/min/ml) activity, significantly different among them. Repeated treatment with AE reduced the mean systolic blood pressure (121.7+/-0.5 mm Hg) by 20 mm Hg after 14 days. The hypotension was reversed upon washout 60 days afterwards. Likely, repeated captopril administration decreased blood pressure by 20 mm Hg throughout treatment in all groups. After 30 days treatment with AE (0.5 g/kg/bid, p.o.) the plasma ACE activity was unchanged in any experimental group. After captopril (50 mg/kg/bid, p.o.) administration the plasma ACE activity was inhibited by 50% within 1 h treatment but it was up-regulated by 120% after 12 h in all groups. It is concluded that the hypotension produced by prolonged treatment with AE of C. glaziovii is unrelated to ACE inhibition.
为评估巴西橡胶树标准化水提取物(AE)对血浆血管紧张素I转化酶(ACE-EC 3.4.15.1)活性的影响,将大鼠单次给予AE(1 g/kg,口服)或重复给予(0.5 g/kg/每日两次,口服),持续60天。卡托普利(50 mg/kg,口服)用作同一批动物的阳性对照。通过直接从股动脉记录血压(单次给药),或通过尾套法间接记录清醒大鼠的血压(重复给药)来观察对血压的影响。使用Hypuril-组氨酸-亮氨酸作为底物,通过荧光分光光度法测定血浆ACE活性。单次给予AE后24小时内,动脉血压、心率和血浆ACE活性均无明显改变。相比之下,卡托普利治疗组大鼠在给药后30分钟至24小时内,血压降低7%-16%,心率增加10%-20%。卡托普利给药后的ACE活性呈现双重反应:给药后30分钟出现即时抑制,峰值为抑制,24小时后缓慢逆转至上调32%。为关联重复给予任一化合物后的药物效应,将血压正常的大鼠分为三组:高ACE活性组(48.8±2.6 nmol/分钟/毫升)、中等ACE活性组(39.4±1.4 nmol/分钟/毫升)和低ACE活性组(23.5±0.6 nmol/分钟/毫升),三组之间差异显著。重复给予AE治疗14天后,平均收缩压(121.7±0.5 mmHg)降低了20 mmHg。60天后停药,低血压状态逆转。同样,在整个治疗过程中,重复给予卡托普利使所有组的血压降低20 mmHg。用AE(0.5 g/kg/每日两次,口服)治疗30天后,任何实验组的血浆ACE活性均未改变。给予卡托普利(50 mg/kg/每日两次,口服)后,治疗1小时内血浆ACE活性被抑制50%,但12小时后所有组均上调120%。得出结论:长期用巴西橡胶树AE治疗产生的低血压与ACE抑制无关。