Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction
Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction
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DOI：
10.1097/fjc.0b013e318177090d
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发表时间：
2008-06-01
影响因子：
3
通讯作者：
Leenen, Frans H. H.
中科院分区：
文献类型：
--
作者：
Ahmad, Monir;White, Roselyn;Leenen, Frans H. H.
背景：大脑肾素-血管紧张素系统对大鼠心肌梗死（MI）后进行性左心室（LV）功能障碍有显着影响。本研究评估了中枢与外周加中枢血管紧张素转换酶 (ACE) 阻断对 MI 后交感神经活性、左心室解剖和功能的影响。方法：MI 后用亲脂性 ACE 抑制剂群多普利 5 mg/kg/天或亲水性阻断剂赖诺普利 50 mg/kg/天治疗 Wistar 大鼠 4 周。 mg/kg/天，每日一次皮下注射，或以0.1 mg/kg/天的赖诺普利中心输注。结果：在最后一次给药后24小时，皮下注射群多普利对大脑和肾脏造成70%至80%的ACE抑制；赖诺普利导致的症状减少 10% 至 20%。赖诺普利的中枢输注可对脑 ACE 产生 70% 的抑制作用，并对肾脏产生最小 (6%) 的抑制作用。所有三种治疗均类似地改善了交感神经反应性和动脉压力反射功能。所有三种治疗均降低了心脏 AngI 和 II，并同样减弱了左心室舒张末压、周长和纤维化的增加。两种皮下注射治疗均进一步降低了左心室收缩压峰值和 dP/dt(max)，而 icv 赖诺普利则没有引起任何变化。结论：尽管外周阻滞程度存在显着差异，但所有三种治疗均相似地影响交感神经活动，并降低 MI 后心脏 Ang II、前负荷和重构。人们可能推测中枢和外周 ACE 介导的机制是连续的，因此仅注意到外周 ACE 阻断的微小额外影响。
Background: The brain renin-angiotensin system contributes significantly to progressive left ventricular (LV) dysfunction in rats after myocardial infarction (MI). The present study evaluated the effects of central versus peripheral plus central angiotensin-converting enzyme (ACE) blockade on sympathetic activity, and LV anatomy and function after MI.Methods: Wistar rats were treated for 4 weeks after MI with the lipophilic ACE inhibitor trandolapril at 5 mg/kg/day or the hydrophilic blocker lisinopril at 50 mg/kg/day by once daily subcutaneous injection, or with a central infusion of lisinopril at 0.1 mg/kg/day.Results: At 24 hours after the last dose, subcutaneous trandolapril caused 70% to 80% ACE inhibition in both brain and kidneys; lisinopril caused 10% to 20% less. Central infusion of lisinopril caused 70% inhibition of brain ACE and minimal (6%) inhibition in the kidneys. All three treatments similarly improved sympathetic reactivity and arterial baroreflex function. All three treatments lowered cardiac AngI and II, and similarly attenuated the increases in LV end diastolic pressure, circumference, and fibrosis. Both subcutaneous treatments further decreased LV peak systolic pressure and dP/dt(max), whereas icv lisinopril caused no change.Conclusion: Despite marked differences in the extent of peripheral blockade, all three treatments similarly affected sympathetic activity and decreased cardiac Ang II, preload and remodeling after MI. One may speculate that central and peripheral ACE-mediated mechanisms are sequential and therefore only minor additional effects of peripheral ACE blockade are noted.