enalapril and Sarcoidosis

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cattle; Dipeptides; Dogs; Enalapril; Humans; Peptidyl-Dipeptidase A; Rats; Sarcoidosis; Species Specificity; Tissue Distribution

The presence of an intrinsic inhibitor of ACE in blood of approximately 25% of sera submitted for serum ACE assay in the diagnosis and evaluation of patients with sarcoidosis, and the common use of ACE inhibitors (captopril and enalapril) in the treatment of hypertension and congestive heart failure, stimulated these studies to compare the effects of the intrinsic and medicinal inhibitors upon serum ACE activity. Since the intrinsic ACE inhibitor in man is affected by serum dilution (inhibition is reversed) and by dialysis (inhibition becomes irreversible), these manipulations were also studied with medicinal inhibitors to provide guidelines for suspecting their presence in submitted serum samples without an accompanying history. Enalapril was found to have delayed onset of action after oral administration (1-2 hours), and was even further delayed (4 hours) when the intrinsic inhibitor also happened to be present. Inhibition by enalapril was not attenuated with refrigerated storage, with dilution or with dialysis of the serum. Captopril had a more rapid time of onset of ACE inhibition, but its inhibitory activity was markedly reduced with refrigerated storage of the serum; patients showed either a short half-life for the effect (1-4 days) or a prolonged half-life (10-17 days). Inhibitory activity of captopril was reversed following dilution of serum or following dialysis. The reversal of inhibition by captopril following dialysis, therefore, differed from the effect of dialysis on the intrinsic ACE inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Enzyme Tests; Dialysis; Enalapril; Humans; Peptidyl-Dipeptidase A; Sarcoidosis

We describe a new principle for the determination of enzymes, here applied to angiotensin-converting enzyme (ACE, EC 3.4.15.1) in human serum. The enzyme inhibitor binding assay is based on specific binding of labeled inhibitor to the active center of the enzyme. Serum (10-15 microL) is incubated with 125I-labeled ACE inhibitor (" 351A ," a p- hydroxybenzamidine derivative of N-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline) at pH 7.0 at 37 degrees C for 2 h in a non-equilibrated system. Inhibitor bound to ACE is separated by adsorption to coated charcoal, the radioactivity remaining in the supernate is counted, and the ACE value is calculated from a standard curve. Sensitivity for ACE in serum is 200 U/L, corresponding to 5.0 ng of ACE purified from human lung. The coefficient of variation was 3.9% within assay, and 6.4% between assays for normal ACE activities. Correlation with a comparison spectrophotometric method (Am J Med 59: 363-372, 1975) for ACE assay was excellent (r = 0.98) in 59 samples from healthy subjects and from patients with various diseases including active sarcoidosis. The novel assay principle presented here is simple and specific, and can be extended to use with various biological fluids and tissues, and to other enzymes as well.

Topics: Angiotensin-Converting Enzyme Inhibitors; Binding, Competitive; Chlorides; Dipeptides; Enalapril; Humans; Hydrogen-Ion Concentration; Methods; Neoplasms; Peptidyl-Dipeptidase A; Sarcoidosis; Sulfates