Baker C R, Little A D, Little G H, Canizaro P C, Behal F J
Department of Surgery, Texas Tech University School of Medicine, Lubbock 79430.
Circ Shock. 1991 Jan;33(1):37-47.
Bradykinin (BK) in an asanguinous salt solution was perfused through intact rat lung. BK concentration varied from 0.0015 to 89 microM. Below 17 microM, the amount degraded was greater than or equal to 90% of the dose. The BK fragment distributions expressed as a percentage of the BK dose degraded were constant. The BK fragments formed and percentage yields were Pro-Pro (2-3) 49%, Arg-Pro-Pro-Gly-Phe (1-5) 32%, Pro-Pro-Gly-Phe-Ser-Pro (2-7) 6%, Arg-Pro-Pro-Gly-Phe-Ser-Pro (1-7) 6%, Arg-Pro-Pro (1-3) 3% and residual BK 4%. Above 17 microM, the amount of BK degraded was not proportional to the dose. Captopril and enalaprilat inhibited BK degradation, and their maximum inhibitions were about 50% and 30%, respectively. The percentage yield of the 1-5 fragment was greatly reduced by both inhibitors, but the percentage yields of the 2-3 and 1-8 fragments were moderately increased. It was concluded that (1) the intact rat lung itself has a very large capacity to degrade BK in the range of 2 mumoles/min/kg body weight; (2) two major and several minor enzyme pathways exist to degrade BK; (3) the relative contributions of these pathways to overall BK degradation remain essentially constant over a bradykinin concentration range from 0.0015 to 17 microM; (4) ACE/kininase-II catalyzed hydrolysis is one of the major pathways but is not the single major route for BK degradation; and (5) the other major BK degradation pathway involves enzymes cleaving the Arg1-Pro2 and Pro3-Gly4 bonds of BK.
将无血盐溶液中的缓激肽(BK)灌注到完整的大鼠肺中。BK浓度在0.0015至89微摩尔之间变化。低于17微摩尔时,降解量大于或等于剂量的90%。以降解的BK剂量的百分比表示的BK片段分布是恒定的。形成的BK片段及其百分比产率分别为:Pro-Pro(2-3)49%、Arg-Pro-Pro-Gly-Phe(1-5)32%、Pro-Pro-Gly-Phe-Ser-Pro(2-7)6%、Arg-Pro-Pro-Gly-Phe-Ser-Pro(1-7)6%、Arg-Pro-Pro(1-3)3%以及残余BK 4%。高于17微摩尔时,BK的降解量与剂量不成比例。卡托普利和依那普利拉抑制BK降解,它们的最大抑制率分别约为50%和30%。两种抑制剂都使1-5片段的百分比产率大幅降低,但2-3和1-8片段的百分比产率适度增加。得出的结论是:(1)完整的大鼠肺本身在2微摩尔/分钟/千克体重范围内具有非常大的降解BK的能力;(2)存在两条主要和几条次要的酶途径来降解BK;(3)在缓激肽浓度从0.0015至17微摩尔的范围内,这些途径对总体BK降解的相对贡献基本保持恒定;(4)ACE/激肽酶-II催化的水解是主要途径之一,但不是BK降解的唯一主要途径;(5)另一条主要的BK降解途径涉及切割BK的Arg1-Pro2和Pro3-Gly4键的酶。