Tissue Angiotensin Converting Enzyme Inhibition: Relevant to Clinical Practice?

Accumulating data indicate that tissue and systemic renin-angiotensin systems may coexist. Evidence supporting the existence of local regulatory systems derives from several sources. Firstly, it has been clearly demonstrated that all components of the renin-angiotensin system are detectable in the tissues of organs such as the brain, heart, lung, kidney, testis, and blood vessels. Secondly, many diverse actions of angiotensin II have been defined in different tissues, all of which have a common mechanism: maintaining or increasing vascular tone, blood volume, or both. Evidence supporting the concept that the local and systemic renin-angiotensin systems are functionally independent includes the discrepancy in the time courses of he-modynamic changes and enzyme inhibition following administration of angiotensin-converting enzyme (ACE) inhibitors; and the observation that ACE inhibitor treatment results in decreases in blood pressure in anephric subjects, who have extremely low circulating concentrations of angiotensin II. These and other data suggest that inhibition of tissue ACE may be as, or more, important than its effects on the more easily measured circulating ACE. This raises the question of whether there are differences among ACE inhibitors in their selectivity for one or more organ systems. Some experimental data indicate that the binding affinity and time course of ACE inhibition can vary from one tissue to another, and among individual agents. Several factors can influence the tissue availability of ACE inhibitors, including the plasma concentration of the drug (or ester prodrug); the rate of conversion of ester to diacid and/or the potential for localized conversion; the relative number of plasma and tissue binding sites for the ACE inhibitor; the rate and route of drug elimination; and the lipophilicity of the drug (or its parent ester). Although the prospect of individualizing therapy by prescribing ACE inhibitors with unique profiles of tissue inhibitory activity is attractive, the clinical relevance and utility of regional ACE inhibition and any differences among ACE inhibitors in terms of tissue selectivity requires further investigation. Am J Hypertens 1990;3:266S-272S