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1、血压 = 心排血量 x 周围血管阻力,高血压 = 心排血量增加 和/或 周围血管阻力增加, 前负荷, 体液容量,肾：钠潴留,外源性钠摄入,遗传因素, 心肌收缩力 心率,血管收缩,交感神经系统,肾素- 血管紧张素- 醛固酮系统,Kaplan NM. Curr Opin Nephrol Hypertens 1994,血压的控制,Schlaish MP Hypertension 2004;43:169-75,高血压时交感活性增加,伴糖尿病（DM2）的高血压患者 交感神经兴奋性显著升高,110,100,90,80,70,60,50,40,30,20,10,0,EHT+DM2,EHT,DM2,NT,P,
2、0.001,P,0.01,P,0.001,P,0.001,交感活性(Impulses/100 beats),Huggett et al, Hypetens. 2004,合并代谢综合征（MS）的高血压患者 交感神经兴奋性显著升高,80,60,40,20,0,P0.01,P0.05,P0.01,P0.001,Huggett et al, Hypetens. 2004,交感活性(Impulses/100 beats),无MS和EHT,EHT,MS,MS+EHT,诺贝尔医学奖 1988,James W. Black博士,“200年来继发现洋地黄以来最伟大的发现”,阻滞剂在心血管领域的应用,缺血性心脏病
3、 稳定性心绞痛 不稳定性心绞痛 急性心肌梗塞 高血压 心律不齐 非对称性窦性心动过速 在心房纤颤或扑动中的心室率的控制 阵发性室上性心动过速 室性快速型心律失常/心室纤维性颤动(索 他洛尔) 先天性长 QT 综合征,慢性心力衰竭 肥厚性梗阻性心肌病 主动脉疾病 Marfans -主动脉壁夹层形成 二尖瓣下垂 二尖瓣狭窄 法洛氏四联症 手术期间高危,阻滞剂其他方面的应用,神经学方面 焦虑 特发性震颤 偏头痛预防 戒酒,内分泌病症 甲状腺毒症 嗜铬细胞瘤 (使用 阻滞剂后),胃肠道病症 食管血管曲张 门静脉高血压,眼科方面 青光眼 ( 局部 ),阻滞剂的作用机制 ,抑制过度激活的交感神经 儿茶酚胺
4、对心肌的毒性作用 主要通过 1 受体通路介导 与RAS 间的相互作用 长期治疗 延缓 、逆转心肌重构的生物学效应 冠脉血流有利的重分配,阻滞剂的作用机制 , 减慢心率 即刻作用 改善心肌缺血 增加舒张期灌注 长期作用改善预后 心率是独立的心血管危险因素 抗心律失常作用 自律性、折返激动、触发激动 室颤阈 独有的作用防止猝死,阻滞剂保护伴高血压的2型糖尿病患者,受体阻滞剂/非糖尿病 受体阻滞剂/糖尿病 无受体阻滞剂/非糖尿病 无受体阻滞剂/糖尿病,生存率%,时间（天数）,100,90,80,0,0,60,120,180,240,300,360,Kjekshus J Eur Heart J 199
5、0;11:43,2006年NICE高血压指南 新确诊高血压患者选择药物流程图,2007 ESH/ESC 高血压指南,NICE has advised the use of -blockers only as fourtth line antihypertensive agents. These conclusions must be considered with care but also with a critical mind . 2007 ESH/ESC高血压指南,Reappraisal of European guidelines on hypertension management
6、,Box 5. Choice of antihypertensive drugs (1) Large-scale meta-analyses of available data confirm that major antihypertensive drug classes, that is,diuretics, ACE inhibitors, calcium antagonists, angiotensin receptor antagonists, and b-blockers do not differ significantly for their overall ability to
7、 reduce BP in hypertension.,Reappraisal of European guidelines on hypertension management,Box 5. Choice of antihypertensive drugs (2) There is also no undisputable evidence that major drug classes differ in their ability to protect against overall cardiovascular risk or cause-specific cardiovascular
8、 events, such as stroke and myocardial infarction. The 2007 ESH/ESC guidelines conclusion that diuretics, ACE inhibitors, calcium antagonists, angiotensin receptor antagonists, and b-blockers can all be considered suitable for initiation of antihypertensive treatment, as well as for its maintenance,
9、Reappraisal of European guidelines on hypertension management,Box 5. Choice of antihypertensive drugs (4) Each drug class has contraindications as well favorable effects in specific clinical settings. The choice of drug(s) should be made according to this evidence. The traditional ranking of drugs i
10、nto first, second, third, and subsequent choice, with an average patient as reference, has now little scientific and practical justification and should be avoided.,Reappraisal of European guidelines on hypertension management,Box 6. Combination therapy (6)Despite trial evidence of outcome reduction,
11、 the -blocker/diuretic combination favors the development of diabetes and should thus be avoided, unless required for other reasons, in predisposed patients.,Reappraisal of European guidelines on hypertension management,Box 7. Antihypertensive treatment in the elderly (2) Data from meta-analyses do
12、not support the claim that antihypertensive drug classes significantly differ in their ability to lower BP and to exert cardiovascular protection, both in younger and in elderly patients. The choice of the drugs to employ should thus not be guided by age. Thiazide diuretics, ACE inhibitors, calcium
13、antagonists, angiotensin receptor antagonists, and -blockers can be considered for initiation and maintenance of treatment also in the elderly.,Reappraisal of European guidelines on hypertension management,Box 8. Antihypertensive treatment in diabetic patients (3) Meta-analyses of available trials s
14、how that in diabetes all major antihypertensive drug classes protect against cardiovascular complications, probably because of the protective effect of BP lowering per se. They can thus all be considered for treatment.,-阻滞剂降压的最佳人群, 冠心病（ 心绞痛 、 ACS 、 心肌梗死 、 CAD二级预防 ） 糖尿病 慢性稳定性收缩性心力衰竭 室上性和室性心律失常（快速性） 高血压伴冠心病危险因素者？ 高血压伴心率增快者 社会心理应激者 焦虑等精神压力增加者 主动脉夹层 肥厚性心肌病 二尖瓣脱垂 高循环动力状态（甲亢、高原） 原发性震颤 偏头痛：缓解率高达60-80%, 脂溶性 无 I SA 1-选择性或非选择性？,受体阻滞剂的选择应用,总 结,交感神经活性-在高血压、冠心病、CVD发生、发展中起着关键的作用，并早于RAS 等的激活 阻滞剂降压疗效并不弱于其他降压药物，可以用于高血压患者（包括老年人）的初始和维持治疗 阻滞剂抑制交感活性所产生的心血管保护作用是其它类药物所无法取代的，尤其在合并冠心病、心力衰竭和严重心律失常患者,Thanks,