Danser A H, Chowdury S, de Lannoy L M, van der Giessen W J, Saxena P R, Schalekamp M A
Cardiovasculair Onderzoeksinstituut Erasmus University Rotterdam (COEUR), The Netherlands.
Cardiovasc Res. 1995 Jun;29(6):789-95.
The aims were (1) to quantitate angiotensin I to II conversion on the endothelial surface and at deeper sites in isolated arteries, (2) to assess whether the angiotensin II that is formed at deeper sites is released into the vascular lumen, and (3) to examine whether enzymes other than angiotensin converting enzyme (ACE) are involved in vascular angiotensin I to II conversion.
Metabolism of [125I]-angiotensin I was studied in isolated perfused porcine coronary and carotid arteries after luminal administration of the labelled peptide (in the perfusion fluid) and after adventitial administration (in the organ bath). Measurements were made both in the presence and in the absence of captopril.
[125I]-angiotensin II was a major metabolite and its formation was virtually completely blocked by captopril, after both luminal and adventitial administration of [125I]-angiotensin I. In coronary arteries (n = 8), the [125I]-angiotensin I to II conversion rate after adventitial administration was about half that after luminal administration. In coronary arteries (n = 6) the conversion rate after adventitial administration was 10-20 times lower than after luminal administration. Degradation of [125I]-angiotensin I into peptides other than [125I]-angiotensin II was also observed, with both luminal and adventitial administration. No [125I]-angiotensin I or II was released into the organ bath after luminal administration of [125I]-angiotensin I, and very little [125I]-angiotensin I and II entered the lumen after adventitial administration of [125I]-angiotensin I.
(1) Vascular angiotensin I to II conversion is not limited to the endothelial surface. (2) ACE is the most important, if not the only, enzyme responsible for vascular angiotensin I to II conversion. (3) If angiotensin I and II are formed in the adventitia or media, little of these peptides will enter the vascular lumen.
本研究旨在(1) 定量分析分离动脉内皮表面及更深层部位血管紧张素I向II的转化；(2) 评估在更深层部位形成的血管紧张素II是否释放到血管腔中；(3) 研究除血管紧张素转换酶(ACE)外，其他酶是否参与血管紧张素I向II的转化。
在离体灌注的猪冠状动脉和颈动脉中，通过管腔内给药（在灌注液中）和外膜给药（在器官浴中）标记肽后，研究[125I] - 血管紧张素I的代谢。在有和没有卡托普利的情况下进行测量。
[125I] - 血管紧张素I管腔内给药和外膜给药后，[125I] - 血管紧张素II均为主要代谢产物，其形成几乎完全被卡托普利阻断。在冠状动脉(n = 8)中，外膜给药后[125I] - 血管紧张素I向II的转化率约为管腔内给药后的一半。在冠状动脉(n = 6)中，外膜给药后的转化率比管腔内给药低10 - 20倍。管腔内给药和外膜给药后均观察到[125I] - 血管紧张素I降解为除[125I] - 血管紧张素II之外的肽。[125I] - 血管紧张素I管腔内给药后，无[125I] - 血管紧张素I或II释放到器官浴中，[125I] - 血管紧张素I外膜给药后，极少[125I] - 血管紧张素I和II进入管腔。
(1) 血管紧张素I向II的转化不限于内皮表面。(2) ACE即使不是唯一，也是负责血管紧张素I向II转化的最重要的酶。(3) 如果血管紧张素I和II在外膜或中膜中形成，这些肽很少会进入血管腔。
