Uresin Y, Mehtar Bozkurt M, Sabirli S, Ozunal Z G
Istanbul University, Faculty of Medicine, Department of Pharmacology, 34390 Capa Istanbul, Turkey.
Expert Rev Cardiovasc Ther. 2007 Sep;5(5):835-49. doi: 10.1586/14779072.5.5.835.
The suppression of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been proven in many studies to treat hypertension and reduce cardiovascular events; however, reducing angiotensin I receptor stimulation results in the loss of the negative-feedback signal, leading to increased plasma renin activity. Numerous direct renin inhibitors were synthesized, but abandoned owing to low potency, poor bioavailability and short half-life. Aliskiren, a direct renin inhibitor of a novel structural class, inhibits the activity of the renin produced and, thus, its capacity to form angiotensin I, as measured by plasma renin activity. Aliskiren has been recently shown to be efficacious in hypertensive patients at once-daily oral dosing with favorable pharmacokinetics and the potential to improve end-organ protection.
许多研究已证实，血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂对肾素-血管紧张素系统的抑制作用可用于治疗高血压并减少心血管事件；然而，减少血管紧张素I受体刺激会导致负反馈信号丧失，从而导致血浆肾素活性增加。人们合成了许多直接肾素抑制剂，但由于效力低、生物利用度差和半衰期短而被放弃。阿利吉仑是一种新型结构类别的直接肾素抑制剂，它可抑制所产生肾素的活性，进而抑制其形成血管紧张素I的能力，这可通过血浆肾素活性来衡量。最近的研究表明，阿利吉仑对高血压患者每日一次口服给药有效，具有良好的药代动力学特性，并具有改善终末器官保护的潜力。
