RAS药物认识蒙诺.ppt

第一部分 药理作用机制有差异吗? 对AT2和AT4受体的新认识 血管紧张素II 1. 长期AT2刺激的可能后果 Conclusions The experimental findings reviewed in this article point to a need fore a more in-depth understanding of the role of AT2 in the cardiovascular system. On the one hand, selective block- ade of AT1 and resultant over stimulation of AT2 by ARBs may be predicted to have a beneficial effect in mediating vasodilation and controlling BP in hypertension. However, accumulating evidence now suggests that long-term AT2 stimulation might also exert a hypertrophic and antiangio- genic influence on cardiovascular tissues. Thus the long-term consequences of ARB therapy might beless beneficial than has been previously supposed and could even be harmful in some circumstances. The potential consequences of such effects, if found to be clinically important, might include cardiac hypertrophy, vascular fibrosis, and a decrease in neovascularrization in hypoxic tissues such as the myocardium 2. ACEI/ARB与AT4: PAI-1的影响 激肽原 ACEI阻滞AII生成, 抑制AT4 , 可抑制 PAI-1生成 ARB选择性阻滞AT1 , 但不抑制AT4 ; 反而, 因反馈性使AII增加, 而增强 AT4 ARB通过增强的AT4 , 可使PAI-1增高 ACEI和ARB在纤溶方面有重要差别。这些差别可能与我们认识到的二者对心肌梗死发生危险性有关 Doughlas E. Vaughan,2002 缓激肽: 心血管的有益作用 ACEI增高缓激肽水平 第二部分 循证医学方面有差异? HOPE研究: 高血压高危人群 50岁 n=15245 缬沙坦160mg/d vs 氨氯地平10mg/d △BP 1.8/1.4mmHg 随访4.2年 主要CV联合终点 P=NS 心肌梗死↑19% P=0.02 严重心绞痛↑30% P0.01 CVA ↑13% P=0.08 ARB增加 了MI? 还是 CCB降低 了MI? 在发生AMI方面: ARBs表现如何? Angiotensin receptor blockers and myocardial Infarction These drugs may increase myocardial infarction--and patients may need to be told BMJ. VOLUME 329, 27 NOVEMBER 2004 2. ARB在心力衰竭的治疗 OPTIMAAL研究: 14703例, AMI后0.5~10d, 伴左室功能不全 缬沙坦组: 320mg/d 24.7个月 卡托普利组: 100mg/d 联合组: