Johnston C I
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Victoria, Australia.
Blood Press Suppl. 2000;1:9-13.
Angiotensin II type 1 (AT1) receptor blockers, such as candesartan, are attractive alternatives to ACE inhibitors in the treatment of hypertension and cardiovascular disease. Although angiotensin-converting enzyme (ACE) inhibitors are able to suppress the renin-angiotensin system (RAS), their mechanism of action may limit their clinical utility in the treatment of hypertension. For example, they act as competitive inhibitors of ACE. This means that their effects can be overcome by high levels of angiotensin I, which occur after ACE inhibition due to removal of the negative feedback effect of angiotensin II on renal renin release. ACE inhibitors are also unable to block the production of angiotensin II by non-ACE-mediated pathways. Furthermore, ACE is not a specific enzyme. Its inhibition therefore has effects on other substances, such as bradykinin, leading to the class-specific side effects associated with ACE inhibitors. Candesartan, on the other hand, binds insurmountably to the AT1-receptor, thereby providing more complete blockade of the negative cardiovascular effects of angiotensin II than is possible with ACE inhibitors. The specificity of AT1-receptor blockade also ensures that efficacy is achieved without inducing the side effect of cough that results from the non-specific consequences of ACE inhibition. Preclinical and early clinical studies demonstrate that AT1-receptor blockers produce at least the same degree of target-organ protection as has been demonstrated for ACE inhibitors. Additional benefits of AT1-receptor blockers may arise from the fact that, unlike ACE inhibitors, they do not prevent the activity of angiotensin II on AT2-receptors in the heart, which is thought to reduce cardiac remodelling. From a mechanistic perspective, therefore, AT1-receptor blockers appear to have advantages over ACE inhibitors, in terms of a more complete blockade of angiotensin II effects, while also avoiding the specific side effects associated with ACE inhibition.
血管紧张素II 1型（AT1）受体阻滞剂，如坎地沙坦，在高血压和心血管疾病的治疗中是血管紧张素转换酶（ACE）抑制剂有吸引力的替代药物。虽然ACE抑制剂能够抑制肾素 - 血管紧张素系统（RAS），但其作用机制可能会限制其在高血压治疗中的临床应用。例如，它们作为ACE的竞争性抑制剂起作用。这意味着它们的作用可以被高水平的血管紧张素I克服，血管紧张素I在ACE抑制后由于血管紧张素II对肾素释放的负反馈作用被消除而出现。ACE抑制剂也无法阻断非ACE介导途径产生的血管紧张素II。此外，ACE不是一种特异性酶。因此其抑制作用会对其他物质产生影响，如缓激肽，导致与ACE抑制剂相关的类特异性副作用。另一方面，坎地沙坦与AT1受体不可逆结合，从而比ACE抑制剂更能完全阻断血管紧张素II的负面心血管效应。AT1受体阻断的特异性还确保了在不引起因ACE抑制的非特异性后果导致的咳嗽副作用的情况下实现疗效。临床前和早期临床研究表明，AT1受体阻滞剂产生的靶器官保护程度至少与ACE抑制剂已证明的相同。AT1受体阻滞剂的额外益处可能源于这样一个事实，即与ACE抑制剂不同，它们不会阻止血管紧张素II对心脏中AT2受体的作用，而这被认为可减少心脏重塑。因此，从机制角度来看，AT1受体阻滞剂在更完全阻断血管紧张素II效应方面似乎比ACE抑制剂具有优势，同时还避免了与ACE抑制相关的特定副作用。
