Corbier A, Lecaque D, Secchi J, Depouez B, Hamon G
Roussel UCLAF, Romainville, France.
J Cardiovasc Pharmacol. 1994;23 Suppl 4:S26-9.
The effects of the angiotensin-converting enzyme inhibitor trandolapril were studied using a Goldblatt (two-kidney, one-clip) rat model of renovascular hypertension after 4 weeks of oral treatment at 0.3 or 1 mg/kg/day. The effects of trandolapril on blood pressure and on cardiac and vascular hypertrophy were analyzed in comparison with the control group. Trandolapril produced a rapid, dose-dependent decrease in blood pressure, which plateaued after 2 weeks of treatment. Complete normalization of blood pressure was observed at a daily dose of 1 mg/kg. Dose-dependent inhibition of cardiac hypertrophy was also observed, heart:body weight ratio being decreased by 17 and 30% at 0.3 and 1 mg/kg, respectively, leading to a normalization of this parameter at the higher dose compared with normotensive controls. Similarly, trandolapril produced a marked decrease in vascular wall hypertrophy in both the mesenteric artery and the aorta. Indeed, complete normalization of media thickness was observed, compared with the normotensive control group, at 1 mg/kg of trandolapril. These results show that short-term treatment with trandolapril can induce complete regression of cardiac and vascular hypertrophy, which is associated with the development of renal hypertension.
在使用Goldblatt(两肾一夹)肾血管性高血压大鼠模型的实验中,研究了血管紧张素转换酶抑制剂群多普利的作用。大鼠口服群多普利,剂量为0.3或1mg/kg/天,持续4周。与对照组相比,分析了群多普利对血压以及心脏和血管肥大的影响。群多普利使血压迅速下降,且呈剂量依赖性,治疗2周后趋于平稳。每日剂量为1mg/kg时,血压完全恢复正常。还观察到群多普利对心脏肥大有剂量依赖性抑制作用,0.3和1mg/kg剂量下心脏与体重比分别降低了17%和30%,与正常血压对照组相比,高剂量时该参数恢复正常。同样,群多普利使肠系膜动脉和主动脉的血管壁肥大明显减轻。实际上,与正常血压对照组相比,群多普利剂量为1mg/kg时,中膜厚度完全恢复正常。这些结果表明,群多普利短期治疗可使与肾性高血压相关的心脏和血管肥大完全消退。