Compartmentalization of angiotensin II generation in the dog heart - Evidence for independent mechanisms in intravascular and interstitial spaces
Compartmentalization of angiotensin II generation in the dog heart - Evidence for independent mechanisms in intravascular and interstitial spaces
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DOI：
10.1172/jci119529
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发表时间：
1997-07-15
影响因子：
15.9
通讯作者：
Oparil, S
中科院分区：
文献类型：
--
作者：
DellItalia, LJ;Meng, QC;Oparil, S
血管紧张素转换酶抑制剂具有有益作用，其可能通过减少血管紧张素II（ANG II）的产生来介导。在这项研究中，我们首次测量了心脏间质液（ISF）空间中的ANG I和ANG II水平。在基线时、静脉输注ANG I期间获得ISF和主动脉血浆ANG I和II水平（5 μ M，0.1 ml/min，60 min），并在ANG I +血管紧张素转换酶抑制剂卡托普利（cap）（2.5 mM，0.1 ml/min，60 min），使用插入左心室心肌的微透析探针（3-4个探针/狗）获得ISF样品。ANC I使平均动脉压从102+/-3（SEM）增加到124+/-3 mmHg（P < 0.01）;添加cap使MAP降低到95+/-3 mmHg（P < 0.01）。ANG I输注增加主动脉血浆ANG I和ANG II（pg/ml）（ANG I = 101+/-129至370+/-158 pg/ml，P < 0.01; ANG II = 22+/-40至466+/-49，P < 0.01）;增加上限进一步增加ANG I（1，790 +/-158，P < 0.01）和降低ANG II（33+/-49，P < 0.01），ISF ANG I和ANG II水平（pg/ml）比血浆水平高100倍以上，且与基线相比无变化（8，122 +/-528和6，333 +/-677），ANG 1期间（8，269 +/-502和6，139 +/-695）或ANG I +上限（8，753 +/-502和5，884 +/-695），在ISF中发现非常高的ANG I和ANG II水平，不受IV ANG I或cap影响的血管内空间的ANG II产生和/或降解表明心脏中的ANG II产生和/或降解是区室化的，并由间质和血管内空间中的不同酶机制介导。
Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 mu M, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs, ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANC I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I(1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01), ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG 1(8,269+/-502 and 6,139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695), The finding of very high ANG I and ANG II levels in the ISF vs, intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.