Borghi C, Boschi S, Ambrosioni E, Melandri G, Branzi A, Magnani B
Department of Clinical Pharmacology and Therapeutics, University of Bologna, Italy.
J Clin Pharmacol. 1993 Jan;33(1):40-5. doi: 10.1002/j.1552-4604.1993.tb03901.x.
Angiotensin-converting enzyme (ACE) inhibitors have been designed to block the renin-angiotensin system and can represent an effective therapeutic approach in those settings where such a system is active, such as myocardial infarction. In a randomized placebo-controlled study, 10 patients with acute myocardial infarction allocated to treatment with increasing doses of zofenopril calcium and 10 patients allocated to placebo were studied in hospital, within 24 hours from symptoms, during 11 sampling periods to assess the time course of ACE inhibition and renin-angiotensin-aldosterone blockade. Zofenopril administration was followed by a dose-dependent inhibition of in vitro ACE activity (7.5 mg, 65%; 15 mg, 89%; 30 mg, 94.5%) and a progressive increase in plasma active renin. Conversely, plasma aldosterone decreased during the first 3 days of treatment and then returned toward baseline values, as did blood pressure, despite a persistent inhibition of ACE. The present data suggest the existence of an interesting dissociation between the time-course of ACE inhibition and that of blockade of the renin-angiotensin system in patients with acute myocardial infarction. This discrepancy could arise from the combination of an only partial in vivo ACE inhibition and the compensatory increase in plasma renin that occurs during treatment with ACE inhibitors. A better understanding of this relationship would seem to be useful in addressing the correct use of ACE inhibitors in patients with acute myocardial injury.
血管紧张素转换酶（ACE）抑制剂旨在阻断肾素-血管紧张素系统，在该系统活跃的情况下，如心肌梗死，可作为一种有效的治疗方法。在一项随机安慰剂对照研究中，对10例急性心肌梗死患者给予递增剂量的佐芬普利钙治疗，另10例患者给予安慰剂，在症状出现后的24小时内住院研究，共进行11个采样期，以评估ACE抑制和肾素-血管紧张素-醛固酮阻断的时间进程。给予佐芬普利后，体外ACE活性呈剂量依赖性抑制（7.5毫克，65%；15毫克，89%；30毫克，94.5%），血浆活性肾素逐渐增加。相反，治疗的前3天血浆醛固酮下降，然后恢复到基线值，血压也是如此，尽管ACE持续受到抑制。目前的数据表明，急性心肌梗死患者中ACE抑制的时间进程与肾素-血管紧张素系统阻断的时间进程之间存在有趣的分离。这种差异可能源于体内ACE仅部分抑制与ACE抑制剂治疗期间血浆肾素代偿性增加的综合作用。更好地理解这种关系似乎有助于正确使用ACE抑制剂治疗急性心肌损伤患者。
