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 hemodynamic 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lees
K R
KR
University Department of Medicine & Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland.
MacFadyen
R J
RJ
Reid
J L
JL
D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A