Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
J Hypertens. 2010 Oct;28(10):2145-55. doi: 10.1097/HJH.0b013e32833d01ae.
The blood pressure-lowering effect of the renin inhibitor aliskiren equals that of angiotensin-converting enzyme (ACE) inhibitors and angiotensin (Ang) II type 1 (AT1) receptor blockers. Whether aliskiren offers end-organ protection remains to be investigated. Here, we compared the cardiac effects of aliskiren, the AT1 receptor blocker irbesartan and the ACE inhibitor captopril in spontaneously hypertensive rats (SHR) at equi-hypotensive doses.
SHR were treated for 1-3 weeks with vehicle, aliskiren, captopril or irbesartan (100, 3 and 15 mg/kg per day, respectively) using an osmotic minipump, and compared to vehicle-treated Wistar-Kyoto (WKY) controls. All drugs lowered (but not normalized) mean arterial pressure in SHR equi-effectively, as monitored by radiotelemetry, without altering heart rate. All drugs also reduced the increased cardiomyocyte area in SHR, and tended to normalize the elevated brain natriuretic peptide plasma levels. In the Langendorff set-up, all drugs normalized the diminished endothelium-dependent vasodilator response to bradykinin in SHR. Moreover, aliskiren and irbesartan, but not captopril, decreased the enhanced coronary Ang II response in SHR. Aliskiren reduced plasma renin activity and the plasma and tissue angiotensin levels at 1 week of treatment; yet, after 3 weeks of aliskiren treatment only the cardiac angiotensin levels remained suppressed, whereas no tissue angiotensin reductions were seen with captopril or irbesartan.
For a given decrease in blood pressure, aliskiren improves coronary endothelial function and decreases cardiac hypertrophy in SHR to at least the same degree as ACE inhibition and AT1 receptor blockade. In addition, aliskiren diminishes the enhanced Ang II response in the coronary circulation of SHR and offers superior long-term cardiac angiotensin suppression.
肾素抑制剂阿利克仑的降压效果等同于血管紧张素转换酶（ACE）抑制剂和血管紧张素（Ang）II 型 1（AT1）受体阻滞剂。阿利克仑是否能提供靶器官保护作用仍有待研究。在此，我们在等降压剂量下比较了阿利克仑、AT1 受体阻滞剂厄贝沙坦和 ACE 抑制剂卡托普利在自发性高血压大鼠（SHR）中的心脏效应。
使用渗透微型泵，将 SHR 分别用载体、阿利克仑、卡托普利或厄贝沙坦（每天 100、3 和 15mg/kg）治疗 1-3 周，并与载体处理的 Wistar-Kyoto（WKY）对照进行比较。所有药物通过无线电遥测监测，在 SHR 中均有效降低（但未正常化）平均动脉压，而不改变心率。所有药物还降低了 SHR 中增加的心肌细胞面积，并倾向于使升高的脑钠肽血浆水平正常化。在 Langendorff 装置中，所有药物均使 SHR 中减弱的内皮依赖性缓激肽介导的血管舒张反应正常化。此外，阿利克仑和厄贝沙坦，但不是卡托普利，降低了 SHR 中增强的冠状动脉 Ang II 反应。阿利克仑在治疗 1 周时降低了血浆肾素活性以及血浆和组织中的血管紧张素水平；然而，在 3 周的阿利克仑治疗后，只有心脏中的血管紧张素水平仍被抑制，而卡托普利或厄贝沙坦则没有降低组织中的血管紧张素水平。
对于给定的血压降低，阿利克仑可改善 SHR 的冠状动脉内皮功能并降低心脏肥大程度，至少与 ACE 抑制和 AT1 受体阻断作用相同。此外，阿利克仑可降低 SHR 冠状动脉循环中增强的 Ang II 反应，并提供更好的长期心脏血管紧张素抑制作用。
