title: New perspectives in the renin-angiotensin-aldosterone system (RAAS) III: endogenous inhibition of angiotensin converting enzyme (ACE) provides protection against cardiovascular diseases.
abstract: ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151). ACE concentration was found to be in a wide range (47-288 ng/mL). ACE activity decreased with the increasing concentration of the serum albumin (HSA): ACE activity was 56 ± 1 U/L in the presence of 2.4 ± 0.3 mg/mL HSA, compared to 39 ± 1 U/L in the presence of 12 ± 1 mg/mL HSA (values are mean ± SEM). Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74-288 ng/mL, median, 155.2 ng/mL, n = 52) compared to patients with II genotype (range, 47-194 ng/mL, median, 94.5 ng/mL, n = 28) while the difference in ACE activities was only 32% (range, 27.3-59.8 U/L, median, 43.11 U/L, and range 15.6-55.4 U/L, median, 32.74 U/L, respectively) in the presence of 12 ± 1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype) and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5 ± 0.5 mg/mL) or other endogenous inhibitors. Main implications are that (1) physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2) angiotensin II elimination may have a significant role in angiotensin II related pathologies.
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Fagyas
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Úri
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Ivetta M
authors.initials: IM
authors.lastname: Siket
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Daragó
authors.affiliation: Department of Neurology, University of Debrecen, Debrecen, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Boczán
authors.affiliation: Institute of Internal Medicine, Division of Nephrology, University of Debrecen, Debrecen, Hungary.
authors.forename: Emese
authors.initials: E
authors.lastname: Bányai
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Édes
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood*; D001794:Blood Pressure / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012709:Serum Albumin; D000804:Angiotensin II; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A