Richard V, Joannides R, Henry J P, Mulder P, Mace B, Guez D, Schiavi P, Thuillez C
Department of Pharmacology (VACOMED-IFRMP 23, Rouen University Medical School, France.
J Hypertens. 1996 Dec;14(12):1447-54. doi: 10.1097/00004872-199612000-00010.
The present study was designed to test the effects of chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor (perindopril) and of the diuretic indapamide in spontaneously hypertensive rats (SHR).
Adult SHR were treated with placebo or increasing doses of the combination of the drugs (0.3, 1 and 3 mg/kg per day; ratio of doses 0.32). In a separate set of experiments, the effects of the drugs combined (1 mg/kg per day) was compared with those induced by each drug alone.
The drug combination dose-dependently decreased systolic blood pressure and its hypotensive effect was more marked than those induced by each treatment administered alone (untreated 208 +/- 5 mmHg, indapamide 185 +/- 5 mmHg, perindopril 150 +/- 3 and the combination 123 +/- 7 mmHg). A 12-week treatment with the drug combination (1 mg/kg per day) was not accompanied by any change in diuresis or urinary excretion of Na or K. The same treatment decreased cardiac hypertrophy and collagen. At the vascular level, the drug combination decreased aortic, carotid and femoral media cross-sectional areas, as well as aortic and carotid collagen density. This latter effect was accompanied by a significant increase in carotid artery compliance assessed in vivo at constant pressure. Finally, in isolated aortae, chronic combined drug treatment was associated with an increased basal release of nitric oxide and a decrease in the hypertension-induced endothelium-dependent contractions in response to acetylcholine.
These experiments suggest that chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor and a diuretic such as indapamide may be of value in the treatment of hypertension.
本研究旨在测试低剂量血管紧张素转换酶抑制剂（培哚普利）与利尿剂吲达帕胺联合长期治疗对自发性高血压大鼠（SHR）的影响。
成年SHR接受安慰剂或递增剂量的药物组合治疗（每天0.3、1和3mg/kg；剂量比为0.32）。在另一组实验中，将联合用药（每天1mg/kg）的效果与每种药物单独使用的效果进行比较。
药物组合剂量依赖性地降低收缩压，其降压效果比单独使用每种药物更显著（未治疗组208±5mmHg，吲达帕胺组185±5mmHg，培哚普利组150±3mmHg，联合用药组123±7mmHg）。联合用药（每天1mg/kg）进行12周治疗后，利尿、尿钠或尿钾排泄均无变化。相同治疗降低了心脏肥大和胶原蛋白含量。在血管水平，药物组合减小了主动脉、颈动脉和股动脉中层横截面积，以及主动脉和颈动脉胶原蛋白密度。后一种效应伴随着在恒定压力下体内评估的颈动脉顺应性显著增加。最后，在离体主动脉中，慢性联合药物治疗与一氧化氮基础释放增加以及高血压诱导的对乙酰胆碱的内皮依赖性收缩减少有关。
这些实验表明，低剂量血管紧张素转换酶抑制剂与利尿剂如吲达帕胺联合长期治疗可能对高血压治疗有价值。
