Compartmentalization of angiotensin II generation in the dog heart - Evidence for independent mechanisms in intravascular and interstitial spaces

被引:175
作者
DellItalia, LJ
Meng, QC
Balcells, E
Wei, CC
Palmer, R
Hageman, GR
Durand, J
Hankes, GH
Oparil, S
机构
[1] UNIV ALABAMA, BIRMINGHAM VET AFFAIRS MED CTR, BIRMINGHAM, AL 35294 USA
[2] UNIV ALABAMA, DEPT MED, DIV CARDIOVASC DIS, BIRMINGHAM, AL 35294 USA
[3] UNIV ALABAMA, DEPT PHYSIOL & BIOPHYS, BIRMINGHAM, AL 35294 USA
[4] AUBURN UNIV, COLL VET MED, AUBURN, AL 36849 USA
关键词
angiotensin-converting enzyme inhibitors; left ventricular function; angiotensins; heart; heart hypertrophy;
D O I
10.1172/JCI119529
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:253 / 258
页数:6
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