第24章作用于肾素-血管紧张素-醛固酮系统的药物-双语精编版.pptx

第 24 章 肾素-血管紧张素－醛固***系统抑制药
2010年10月
Inhibitors of the renin-angiotensin-aldosterone system
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本次课要求掌握的内容
、作用机理、主要的临床应用和不良反应。
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、作用机理、临床应用和不良反应方面的异同。
，你对靶点发现、确认及与药物研发的关系有何心得？
。
hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy
Pathophysiology
Renin-Angiotensin-Aldosterone System
RAAS
×
×
×
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renin-angiotensin-aldosterone system
History
Components of RAAS
Functions and Effects of RAAS
(RAAS)
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In 1898, Tiegerstedt and Bergman found that crude saline extracts of the kidney contained a pressor substance that they named renin.
History
1898, Tiegerstedt 和 Bergman 发现肾脏的盐水粗提物含有加压物质，他们将其命名为“肾素”。
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Tigerstedt R, Bergman PG: Niere und Kreislauf 肾脏和循环. Skand Arch Physiol 1898; 8:223-271.
1934, Goldblatt 证明收缩肾血管可产生持续的高血压 (renal hypertension)
In 1940, Braun-Menendez(Argentina), Page and Helmer (USA) 分别报道肾素是酶，产生缩血管物质，前者称其为hypertensin ，后者称其为angiotonin.
大约20年后，将此过程中的升压物质命名为血管紧张素angiotensin，血浆中的底物称为 血管紧张素原angiotensinogen.
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In the mid-1950s, a decapeptide and an octape-ptide were recognized. The octapeptide was shown to be the more active form.
decapeptide
octapeptide
angiotensin-converting enzyme(ACE)
enzyme
(Angiotensin I)
(Angiotensin II)
in 1957, synthesized by Schwyzer and Bumpus
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In the early 1970s, important physiological and pathophysiological roles for the RAAS were revealed.
上个世纪七十年代早期，开始认识RAAS的重要的生理和病理生作用。
Physiological roles
Pathohysiological roles
Pharmacological intervention
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Thirst
Converting
enzyme
Pressor effect
Sympathetic
stimulation
ADH secretion
Converting enzyme
antagonist
Captopril enalapril
enalkiren
Remikiren
Aliskiren
Renin inhibitor
Ang II receptor
Antagonist losartan
Aldosterone secretion
Renin
Components of RAAS
Aldosterone secretion
Ang III
Ang IV
Ang 1-7
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