Clozel J P, Véniant M, Hess P, Sprecher U
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Hypertension. 1991 Oct;18(4 Suppl):II8-14. doi: 10.1161/01.hyp.18.4_suppl.ii8.
The goal of the present study was to compare the effects of cilazapril, a new long-acting angiotensin converting enzyme inhibitor, to those of captopril and hydralazine on the coronary vascular bed. For this purpose, spontaneously hypertensive rats were treated for 4 months with either placebo, 10 mg/kg/day cilazapril, 100 mg/kg/day captopril, or 10 mg/kg/day hydralazine. At the end of treatment, maximal coronary blood flow was measured during maximal coronary vasodilation with adenosine in isolated perfused hearts. Cilazapril was the most effective drug in increasing maximal coronary blood flow. Captopril was less effective in improving maximal coronary blood flow but was as effective as cilazapril in reducing cardiac hypertrophy. Hydralazine had an extremely small effect on cardiac hypertrophy and maximal coronary flow reserve. The ranking of efficacy was similar for the reduction of vessel wall hypertrophy in the coronary arteries and arterioles. Because of the higher efficacy of cilazapril compared with captopril, a second experiment was performed in which 10 mg/kg/day cilazapril was compared with 100 mg/kg/day captopril and 300 mg/kg/day captopril after 1 month of treatment. Captopril increased maximal coronary flow and decreased cardiac hypertrophy to the same level as cilazapril only at the highest dose. We conclude that angiotensin converting enzyme inhibitors, in contrast to hydralazine, can increase markedly maximal coronary flow in spontaneously hypertensive rats but that this increase does not always parallel the decrease of cardiac hypertrophy and is closely dose dependent.
本研究的目的是比较新型长效血管紧张素转换酶抑制剂西拉普利与卡托普利和肼屈嗪对冠状血管床的作用。为此，将自发性高血压大鼠分别用安慰剂、10毫克/千克/天西拉普利、100毫克/千克/天卡托普利或10毫克/千克/天肼屈嗪治疗4个月。治疗结束时，在离体灌注心脏中用腺苷进行最大冠脉血管舒张时测量最大冠脉血流量。西拉普利是增加最大冠脉血流量最有效的药物。卡托普利在改善最大冠脉血流量方面效果较差，但在减轻心脏肥大方面与西拉普利效果相同。肼屈嗪对心脏肥大和最大冠脉血流储备的影响极小。在减少冠状动脉和小动脉的血管壁肥大方面，疗效排名相似。由于西拉普利比卡托普利疗效更高，因此进行了第二项实验，在治疗1个月后将10毫克/千克/天西拉普利与100毫克/千克/天卡托普利和300毫克/千克/天卡托普利进行比较。卡托普利仅在最高剂量时才能将最大冠脉血流量增加并将心脏肥大减轻至与西拉普利相同的水平。我们得出结论，与肼屈嗪相比，血管紧张素转换酶抑制剂可显著增加自发性高血压大鼠的最大冠脉血流量，但这种增加并不总是与心脏肥大的减轻平行，且密切依赖剂量。
