Measurement of angiotensin I converting enzyme inhibition in the heart.

摘要: Angiotensin (Ang) I converting enzyme (ACE) inhibitors represent a major advance in the treatment of congestive heart failure, and tissue, rather than circulating ACE, may be their site action. However, assessments tissue ACE inhibition treated patients has not always supported this contention. In these studies, activity was measured homogenates sampled by biochemical methods. present study, using model system, we have examined validity tissue-sampling Functional determined comparing positive inotropic responses to [Pro10]Ang either vehicle-pretreated or inhibitor-pretreated papillary muscles. elicits response, which is entirely dependent on ACE-mediated conversion Ang II. The studied were captopril, enalaprilat, lisinopril, quinaprilat. parallel muscle also [125I]MK-351A (a radiolabeled inhibitor) binding. studies indicate that method significantly underestimated functional hamster muscles (p < 0.001). Kinetic indicated half-time for dissociation [3H]enalaprilat [3H]lisinopril from ventricular 4.5 6.2 minutes, respectively. [3H]quinaprilat biphasic (half-time, 47 90 minutes), indicating two active sites somatic differ ability bind inhibitor. rapid rate inhibitor suggests that, during time taken assay biochemically, becomes "disinhibited," leading an underestimation inhibition. rates partially predictive duration muscles; other factors appeared contribute "tissue trapping" de novo synthesis Quantification its relation drug efficacy must, therefore, involve careful consideration avoid artifacts clinical decision making pathogenic mechanisms involved failure.