Reneland R, Lithell H
Department of Geriatrics, Uppsala University, Sweden.
Blood Press. 1997 Mar;6(2):103-8. doi: 10.3109/08037059709061807.
Research into the exact mechanism and site of action of ACE inhibiting compounds has been hampered by methodological difficulties concerning the quantitation of ACE inhibition in tissues. This paper describes an attempt to address this difficulty. ACE activity in serum and uncentrifuged skeletal muscle homogenates was measured with a fluorometric assay before and during treatment in 24 fosinopril-treated and 26 atenolol-treated hypertensives. The absolute difference in activity between the higher and the lower of two different sample dilutions divided by the mean activity was taken to represent competitive inhibition in the sample, "inhibitor index". The reduction in muscle ACE activity coinciding with fosinopril treatment was not statistically significant (-2.6%, p = 0.68). The inhibitor index, however, increased by 46% (p = 0.045) and no change was seen in the atenolol-treated group (-12%, p = 0.51). The change in muscle inhibitor index (but not the reduction in serum ACE activity) correlated inversely with the change in blood pressure (r = -0.50, p = 0.034) and serum aldosterone (r = -0.54, p = 0.031) in the fosinopril group, but not in the atenolol group. In a second study, serum inhibitor index increased by 0.28 (95% CI 0.24-0.32) in 12 trandolapril-treated, but was unchanged in 11 atenolol-treated patients (+0.0097, 95% CI -0.029-0.048). In conclusion, the present study indicates that the inhibitor index described recognizes physiologically relevant ACE inhibition. The value of the method needs to be investigated further.
由于在组织中定量检测血管紧张素转换酶（ACE）抑制存在方法学上的困难，对ACE抑制化合物的确切作用机制和作用部位的研究受到了阻碍。本文描述了为解决这一困难所做的尝试。在24例服用福辛普利和26例服用阿替洛尔的高血压患者治疗前及治疗期间，采用荧光测定法测量血清和未离心的骨骼肌匀浆中的ACE活性。将两种不同样品稀释度中较高值与较低值之间的活性绝对差值除以平均活性，以代表样品中的竞争性抑制，即“抑制剂指数”。与福辛普利治疗同时出现的肌肉ACE活性降低无统计学意义（-2.6%，p = 0.68）。然而，抑制剂指数增加了46%（p = 0.045），而阿替洛尔治疗组未见变化（-12%，p = 0.51）。福辛普利组肌肉抑制剂指数的变化（而非血清ACE活性的降低）与血压变化（r = -0.50，p = 0.034）和血清醛固酮变化（r = -0.54，p = 0.031）呈负相关，而阿替洛尔组则无此相关性。在第二项研究中，12例服用群多普利的患者血清抑制剂指数增加了0.28（95%可信区间0.24 - 0.32），而11例服用阿替洛尔的患者血清抑制剂指数无变化（+0.0097，95%可信区间 -0.029 - 0.048）。总之，本研究表明所描述的抑制剂指数能够识别生理相关的ACE抑制。该方法的价值有待进一步研究。
