Inhibitor index: a novel method for measuring pharmacological inhibition of angiotensin-converting enzyme.
Research into the exact mechanism and site of action of ACE inhibiting compounds has been hampered by methodological difficulties concerning the quantitation of ACE inhibition in tissues. This paper describes an attempt to address this difficulty. ACE activity in serum and uncentrifuged skeletal muscle homogenates was measured with a fluorometric assay before and during treatment in 24 fosinopril-treated and 26 atenolol-treated hypertensives. The absolute difference in activity between the higher and the lower of two different sample dilutions divided by the mean activity was taken to represent competitive inhibition in the sample, "inhibitor index". The reduction in muscle ACE activity coinciding with fosinopril treatment was not statistically significant (-2.6%, p = 0.68). The inhibitor index, however, increased by 46% (p = 0.045) and no change was seen in the atenolol-treated group (-12%, p = 0.51). The change in muscle inhibitor index (but not the reduction in serum ACE activity) correlated inversely with the change in blood pressure (r = -0.50, p = 0.034) and serum aldosterone (r = -0.54, p = 0.031) in the fosinopril group, but not in the atenolol group. In a second study, serum inhibitor index increased by 0.28 (95% CI 0.24-0.32) in 12 trandolapril-treated, but was unchanged in 11 atenolol-treated patients (+0.0097, 95% CI -0.029-0.048). In conclusion, the present study indicates that the inhibitor index described recognizes physiologically relevant ACE inhibition. The value of the method needs to be investigated further.
Reneland
R
R
Department of Geriatrics, Uppsala University, Sweden.
Lithell
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001262:Atenolol / Q000627:therapeutic use; D002309:Cardiology / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D005470:Fluorometry; D017328:Fosinopril / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology*; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; C052035:trandolapril; D001262:Atenolol; D007703:Peptidyl-Dipeptidase A; D017328:Fosinopril