Scalbert E, Narcisse G, Abdon D, Fauchère J L, Santoni J P
Institut de Recherches Internationales Servier, Neuilly-sur-Seine, France.
J Cardiovasc Pharmacol. 1990 Apr;15(4):676-83.
Adult spontaneously hypertensive rats (SHR) were daily treated for 2 weeks with perindopril [an angiotensin-converting enzyme (ACE) inhibitor] and nitrendipine (a calcium antagonist) alone or in combination. Blood pressure (BP), heart rate (HR), and diuresis were assessed weekly in conscious rats, and systemic and regional hemodynamics were investigated by the microsphere technique at the end of the treatment in anesthetized rats. Both perindopril (2 mg.kg-1.d-1) and nitrendipine (10 mg.kg-1.d-1) decreased BP to the same extent, but perindopril exerted a longer action. The hemodynamic profile of each drug was respectively consistent with the classic ones of ACE inhibitors and calcium antagonists already described in the literature. With combination of the two treatments, effects were at least additive, except that the nitrendipine-induced tachycardia was partially reduced by perindopril. BP reduction was additive, and significant potentiation was shown at the systemic [cardiac index (CI) increase, total peripheral resistance (TPR) decrease] and some regional (hepatic, muscular, and cutaneous vasodilations) levels. These results, which are in agreement with the different mechanisms of action of the two drugs, emphasize the advantage of combining perindopril with nitrendipine for treatment of hypertension.
成年自发性高血压大鼠（SHR）每天接受培哚普利[一种血管紧张素转换酶（ACE）抑制剂]和尼群地平（一种钙拮抗剂）单独或联合治疗，持续2周。每周对清醒大鼠的血压（BP）、心率（HR）和利尿情况进行评估，并在治疗结束时通过微球技术对麻醉大鼠的全身和局部血流动力学进行研究。培哚普利（2mg·kg⁻¹·d⁻¹）和尼群地平（10mg·kg⁻¹·d⁻¹）均能使血压降低至相同程度，但培哚普利的作用持续时间更长。每种药物的血流动力学特征分别与文献中已描述的ACE抑制剂和钙拮抗剂的经典特征一致。两种治疗方法联合使用时，效果至少是相加的，只是培哚普利可部分减轻尼群地平引起的心动过速。血压降低是相加的，并且在全身[心脏指数（CI）增加、总外周阻力（TPR）降低]和一些局部（肝脏、肌肉和皮肤血管舒张）水平显示出显著的协同作用。这些结果与两种药物不同的作用机制一致，强调了培哚普利与尼群地平联合治疗高血压的优势。
