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• W2030244028 abstract "1 We determined apparent Ki constants of two inhibitors, captopril and CL242,817, for pulmonary endothelial-bound angiotensin converting enzyme (ACE) in anaesthetized rabbits. [3H]-benzoyl-Phe-Ala-Pro was used as the substrate. The apparent kinetic parameters Km and Amax (product of Vmax and microvascular plasma volume) were measured, as was the ratio (Amax/Km) (measured under first order reaction conditions) before and 30s after the i.v. administration of captopril 10 nmol kg−1 or CL242,817, 35 nmol kg−1. 2 Under mixed order reaction conditions, ([S] ≥ Km), apparent Km values increased from 12.2 ± 1.9 μm to 32.9 ± 3.3 μm (P < 0.05) in the captopril-treated rabbits and from 9.3 ± 2.3 μm to 45.8 ± 9.8 μm (P < 0.05) in the CL242,817-treated rabbits, indicative of competitive inhibition. However, apparent Amax values decreased from 10.3 ± 2.1 to 4.5 ± 0.8 μmol min−1 (P < 0.05) and 8.9 ± 1.7 to 4.8 ± 0.5 μmol min−1 (P < 0.05), respectively. 3 Under first order reaction conditions ([S] ≪ Km), the Amax/Km ratio decreased from 763 ± 100 to 125 ± 38 ml min−1 (P < 0.05) and 1009 ± 149 to 126 ± 44 ml min−1 (P < 0.05) in the captopril- and CL242,817-treated groups respectively. 4 When the single pass transpulmonary binding of 80 pmol [3H]-RAC-X-65 (an ACE inhibitor) was measured in additional rabbits, a significant (P < 0.05) decrease in RAC-X-65 binding was observed 30 s after captopril (80% decrease) or CL242,817 (85% decrease), a result expected for a loss of catalytically active enzyme mass due to tightly bound captopril or CL242,817. 5 These results indicate that, in vivo, both captopril and CL242,817 are competitive, tight binding inhibitors of lung ACE. Furthermore, they suggest means for evaluating the interaction of other potential ACE inhibitors with the pulmonary endothelial membrane-bound enzyme, in vivo, possibly in phase I clinical trials." @default.
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• W2030244028 date "1990-09-01" @default.
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• W2030244028 title "Inhibition of endothelial-bound angiotensin converting enzyme, in vivo" @default.
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• W2030244028 doi "https://doi.org/10.1111/j.1476-5381.1990.tb12100.x" @default.
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