Lung angiotensin-converting enzyme kinetics from indicator-dilution and constant-infusion methods.
Lung angiotensin-converting enzyme kinetics from indicator-dilution and constant-infusion methods.
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指示剂稀释和恒定输注方法的肺血管紧张素转换酶动力学。
DOI：
10.1152/ajpheart.1990.258.2.h436
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Dawson,CA
中科院分区：
文献类型：
--
作者：
Linehan,JH;Bongard,RD;Roerig,DL;Bronikowski,TA;Dawson,CA
本文比较了血管紧张素转换酶在兔离体肺中对苯甲酰苯丙氨酰-丙氨酰-脯氨酸(BPAP)酶解动力学的三种方法的评价结果。在方法A中，利用四种BPAP输注速率下的动静脉动静脉浓度差来确定浓度对BPAP水解率的影响。在方法B1和B2中，在每次持续输注未标记BPAP的过程中注入微量剂量的[~3H]BPAP，以便利用静脉中的[~H]BPAP浓度来估计静脉中BPAP的浓度和在每个本底浓度下的水解率。在方法C中，注射含有不同数量的未标记BPAP以及示踪剂[~3H]BPAP的三个丸剂，使得每个丸剂产生的浓度和水解率范围可以从[~3H]BPAP的静脉浓度来估计。每种方法都提供了计算最大摄取速率(Vmax)和Km所需的数据，Km是半Vmax时的浓度，假设水解可以用Michaelis-Menten方程表示。然而，每种方法背后的数学模型涉及不同的假设，即毛细血管转运时间和团剂分散的异质性的影响。A、B1、B2和C方法的Vmax平均值分别为180、216、217和200nmol/S，Km值分别为7.8、10.4、8.6和10.0微米。两种方法之间的差异无统计学意义。这些结果表明，相对于导致每种方法随机误差的其他因素，这两种方法之间的理论差异在数量上并没有产生重要的影响。因此，可以根据实际情况在方法之间进行选择。
We compared the results of three methods used to evaluate the kinetics of benzoyl-phenylalanyl-alanyl-proline (BPAP) hydrolysis by angiotensin-converting enzyme in the isolated rabbit lung. In method A, the arteriovenous concentration differences at each of four rates of BPAP infusion were used to determine the effect of concentration on the rate of BPAP hydrolysis. In methods B1 and B2, trace doses of [3H]BPAP were injected during each constant infusion of unlabeled BPAP so that the venous [3H]BPAP concentration could be used to estimate the venous BPAP concentration and the rate of hydrolysis at each background concentration. In method C, three boluses containing different amounts of unlabeled BPAP as well as tracer [3H]BPAP were injected such that each bolus resulted in a range of concentrations and hydrolysis rates that could be estimated from the venous concentrations of [3H]BPAP. Each method provided the data needed to calculate the maximum uptake rate (Vmax) and Km, the concentration at half Vmax, assuming that the hydrolysis can be represented by the Michaelis-Menten equation. However, the mathematical model underlying each method involved different assumptions about the effects of heterogeneity of capillary transit times and bolus dispersion. The mean values of Vmax were 180, 216, 217, and 200 nmol/s and for Km 7.8, 10.4, 8.6, and 10.0 microM for methods A, B1, B2, and C, respectively. The differences between methods were not statistically significant. These results suggest that theoretical differences between the methods did not have a quantitatively important impact relative to other factors contributing random errors to each of the methods. The choice between methods can therefore be made on practical grounds.