BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. OBJECTIVES: To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. METHODS: The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mgenalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment withhydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient's blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. RESULTS:Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. CONCLUSION: Due to the fact that "20% of patients do not respond to ACEI by blood pressure drop," the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.
RCT Entities:
BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. OBJECTIVES: To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. METHODS: The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient's blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. RESULTS:Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. CONCLUSION: Due to the fact that "20% of patients do not respond to ACEI by blood pressure drop," the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.
Authors: Sergei M Danilov; Victoria E Tikhomirova; Olga V Kryukova; Alexander V Balatsky; Naida I Bulaeva; Elena Z Golukhova; Leo A Bokeria; Larisa M Samokhodskaya; Olga A Kost Journal: PLoS One Date: 2018-12-27 Impact factor: 3.240
Authors: Sergei M Danilov; Roman Metzger; Eckhard Klieser; Karl Sotlar; Ilya N Trakht; Joe G N Garcia Journal: PLoS One Date: 2019-12-26 Impact factor: 3.240
Authors: Sergei M Danilov; Alexey V Kadrev; Olga V Kurilova; Victoria E Tikhomirova; Olga V Kryukova; Vadim N Mamedov; David M Kamalov; Natalia V Danilova; Dmitry A Okhobotov; Nurshat M Gayfullin; Valery V Evdokimov; Boris J Alekseev; Olga A Kost; Larisa M Samokhodskaya; Armais A Kamalov Journal: Oncotarget Date: 2019-10-29