人乳内动脉中血管紧张素II形成的双重途径。

Dual pathway for angiotensin II formation in human internal mammary arteries.

作者信息

Voors A A, Pinto Y M, Buikema H, Urata H, Oosterga M, Rooks G, Grandjean J G, Ganten D, van Gilst W H

机构信息

Department of Clinical Pharmacology, University of Groningen, The Netherlands.

出版信息

Br J Pharmacol. 1998 Nov;125(5):1028-32. doi: 10.1038/sj.bjp.0702150.

DOI:10.1038/sj.bjp.0702150

PMID:9846641

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565667/

Abstract

Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convert antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin II formation was due to another enzyme, identified as human heart chymase. In the human vasculature however, the predominance of either ACE or non-ACE conversion of angiotensin I remains unclear. 2. To study the effects of ACE- and chymase-inhibition on angiotensin II formation in human arteries, segments of internal mammary arteries were obtained from 37 patients who underwent coronary bypass surgery. 3. Organ bath experiments showed that 100 microM captopril inhibited slightly the response to angiotensin I (pD2 from 7.09+/-0.11-6.79+/-0.10, P<0.001), while 100 microM captopril nearly abolished the response to [pro10] angiotensin I, a selective substrate for ACE, and the maximum contraction was reduced from 83+/-19%-23+/-17% of the control response (P=0.01). A significant decrease of the pD2 of angiotensin I similar to captopril was observed in the presence of 50 microM chymostatin (pD2 from 7.36+/-0.13-6.99+/-0.15, P<0.039), without influencing the maximum response. In the presence of both inhibitors, effects were much more pronounced than either inhibitor alone, and a 300 times higher dose was needed to yield a significant contraction response to angiotensin I. 4 These results indicate the presence of an ACE and a non-ACE angiontensin II forming pathway in human internal mammary arteries.

摘要

血管紧张素转换酶（ACE）被认为是将血管紧张素I转化为血管活性物质血管紧张素II的主要酶。最近，在人类心脏中发现，大部分血管紧张素II的形成是由另一种酶引起的，这种酶被鉴定为人类心脏糜酶。然而，在人类血管系统中，血管紧张素I由ACE或非ACE转化的优势尚不明确。2. 为了研究ACE抑制和糜酶抑制对人类动脉中血管紧张素II形成的影响，从37例行冠状动脉搭桥手术的患者身上获取了乳内动脉段。3. 器官浴实验表明，100微摩尔卡托普利对血管紧张素I的反应有轻微抑制作用（pD2从7.09±0.11降至6.79±0.10，P<0.001），而100微摩尔卡托普利几乎完全消除了对[脯氨酸10]血管紧张素I（ACE的选择性底物）的反应，最大收缩幅度从对照反应的83±19%降至23±17%（P=0.01）。在存在50微摩尔抑糜酶素的情况下，观察到血管紧张素I的pD2有与卡托普利类似的显著下降（pD2从7.36±0.13降至6.99±0.15，P<0.039），但不影响最大反应。在两种抑制剂同时存在的情况下，作用比单独使用任何一种抑制剂都更明显，并且需要高300倍的剂量才能产生对血管紧张素I的显著收缩反应。4. 这些结果表明人类乳内动脉中存在一条ACE途径和一条非ACE途径来形成血管紧张素II。