Mizuno K, Niimura S, Tani M, Haga H, Inagami T, Fukuchii S
Third Department of Internal Medicine, Fukushima Medical College, Japan.
Am J Hypertens. 1991 Jan;4(1 Pt 2):67S-72S. doi: 10.1093/ajh/4.1.67s.
Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused human umbilical veins was inhibited by the angiotensin-converting enzyme inhibitor captopril. To further investigate the mechanism by which Ang II is generated in the blood vessels of humans, we examined the effects of various inhibitors of the renin-angiotensin system (captopril, delapril, N-acetyl-pepstatin, and human renin inhibitor KRI-1314) on Ang II release from perfused human umbilical cord veins in vitro. Isolated human umbilical veins were perfused with Krebs-Ringer solution, and immunoreactive Ang II released into the perfusate was measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Both captopril and delapril diacid (10(-9) to 5 x 10(-6) mol/L), an active metabolite of delapril hydrochloride, suppressed the Ang II release in a dose-dependent fashion; the maximal percent suppression of Ang II release evoked by these inhibitors (5 x 10(-6) mol/L) was 56% and 64%, respectively, for captopril and delapril. Both N-acetyl-pepstatin (10(-9) to 10(-5) mol/L) and KRI-1314 (10(-9) to 10(-6) mol/L) suppressed Ang II release in a dose-related manner. At a 10(-6) mol/L concentration, KRI-1314 produced a 74% reduction in the basal rate of Ang II release, and a reduction threefold greater than the maximal reduction in basal Ang II release produced by N-acetyl-pepstatin.(ABSTRACT TRUNCATED AT 250 WORDS)
我们先前报道，血管紧张素转换酶抑制剂卡托普利可抑制离体灌注人脐静脉释放免疫反应性血管紧张素II（Ang II）。为进一步研究人体内血管生成Ang II的机制，我们在体外检测了肾素-血管紧张素系统的各种抑制剂（卡托普利、地拉普利、N-乙酰胃蛋白酶抑制剂和人肾素抑制剂KRI-1314）对灌注人脐带静脉释放Ang II的影响。将离体人脐静脉用 Krebs-Ringer 溶液灌注，通过连接到灌注系统的Sep-Pak C18柱直接测量灌注液中释放的免疫反应性Ang II。卡托普利和地拉普利二酸（10(-9)至5×10(-6) mol/L），即盐酸地拉普利的活性代谢产物，均以剂量依赖方式抑制Ang II释放；这些抑制剂（5×10(-6) mol/L）引起的Ang II释放最大抑制百分比，卡托普利和地拉普利分别为56%和64%。N-乙酰胃蛋白酶抑制剂（10(-9)至10(-5) mol/L）和KRI-1314（10(-9)至10(-6) mol/L）均以剂量相关方式抑制Ang II释放。在10(-6) mol/L浓度下，KRI-1314使Ang II释放基础速率降低74%，比N-乙酰胃蛋白酶抑制剂引起的基础Ang II释放最大降低幅度大三倍。（摘要截短于250字）
