Asmar R G, Iannascoli F, Benetos A, Safar M E
Department of Internal Medicine, Broussais Hospital, Paris, France.
J Hypertens Suppl. 1992 Jul;10(5):S13-9.
In treating hypertension the optimal dose of angiotensin converting enzyme (ACE) inhibitor is derived from dose-response curves that relate the quantity of drug taken to the resulting fall in blood pressure; the blood pressure fall reflects a decrease in vascular resistance and hence, a degree of arteriolar vasodilation. However, ACE inhibition dilates not only the small arteries but also the larger calibre arteries, which increases compliance. Given the differences in structure and function of large and small arteries, the optimal drug dose for a given vessel may differ according to the size and structure of the vessel. DOSE-RESPONSE EFFECTS IN CLINICAL STUDIES: Clinical studies indicate that in the brachial artery territory, larger doses are required to obtain arterial dilation than to produce a decrease in vascular resistance. In the aorta, an improvement in arterial compliance and distensibility is governed both by the fall in blood pressure and the drug dose. Finally, for the femoral artery, the degree of arterial dilation is influenced markedly only by the drug dose.
An understanding of the drug dose required to produce a given change in the hypertensive arterial system may have important implications for the control of blood pressure. For a given mean arterial pressure, systolic blood pressure is lower and diastolic blood pressure higher when aortic compliance is increased, a haemodynamic change commonly seen following ACE inhibition. Recent double-blind studies have shown that ACE inhibitors produced a more pronounced decrease in systolic than diastolic blood pressure.
These findings indicate that the optimum doses required to improve the arterial wall in large arteries must be evaluated by long-term antihypertensive therapy.
在治疗高血压时，血管紧张素转换酶（ACE）抑制剂的最佳剂量源自剂量反应曲线，该曲线将所服用药物的量与由此导致的血压下降相关联；血压下降反映了血管阻力的降低，进而反映了一定程度的小动脉血管舒张。然而，ACE抑制不仅会扩张小动脉，还会扩张管径较大的动脉，从而增加顺应性。鉴于大动脉和小动脉在结构和功能上存在差异，针对特定血管的最佳药物剂量可能会因血管的大小和结构而有所不同。
临床研究表明，在肱动脉区域，要实现动脉扩张所需的剂量大于降低血管阻力所需的剂量。在主动脉中，动脉顺应性和扩张性的改善既受血压下降的影响，也受药物剂量的影响。最后，对于股动脉，动脉扩张程度仅明显受药物剂量的影响。
了解在高血压动脉系统中产生特定变化所需的药物剂量可能对血压控制具有重要意义。对于给定的平均动脉压，当主动脉顺应性增加时，收缩压较低而舒张压较高，这是ACE抑制后常见的血流动力学变化。最近的双盲研究表明，ACE抑制剂使收缩压下降比舒张压下降更为明显。
这些发现表明，必须通过长期抗高血压治疗来评估改善大动脉动脉壁所需的最佳剂量。
