• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jclinpathJournal of Clinical PathologyCurrent TOCInstructions for authors
J Clin Pathol. Aug 1983; 36(8): 938–947.
PMCID: PMC498427

Angiotensin-converting enzyme and its clinical significance--a review.

Abstract

There have been considerable advances in understanding the metabolic role of the endothelial lining cells of the blood vessels. Angiotensin-converting enzyme activity is concentrated in these cells, especially those lining the pulmonary circulation. The enzyme exerts control over systemic vascular tone indirectly through the powerful pressor effect of angiotensin II. A number of therapeutic agents are now available which directly inhibit converting enzyme activity and thereby effect a reduction in blood pressure. Macrophages are the source of increased angiotensin-converting enzyme activity commonly found in association with active sarcoidosis. A better understanding of this phenomenon may give fresh insight into this puzzling condition. Pulmonary endothelial metabolism is affected by lung injury and it is likely that in this situation changing activities of serum angiotensin converting enzyme may indicate the extent of damage and the response to therapy. The full clinical significance of serum ACE measurements has yet to be established. However, raised activities have been reported in a number of other conditions and diabetes mellitus and hyperthyroidism are of particular current interest. The numerous methods and reference ranges described in the literature for the measurement of serum ACE activity require further assessment, and there is a clear need for an accepted reference method.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • SKEGGS LT, Jr, MARSH WH, KAHN JR, SHUMWAY NP. The existence of two forms of hypertensin. J Exp Med. 1954 Mar;99(3):275–282. [PMC free article] [PubMed]
  • SKEGGS LT, Jr, MARSH WH, KAHN JR, SHUMWAY NP. The existence of two forms of hypertensin. J Exp Med. 1954 Mar;99(3):275–282. [PMC free article] [PubMed]
  • SKEGGS LT, Jr, KAHN JR, SHUMWAY NP. The preparation and function of the hypertensin-converting enzyme. J Exp Med. 1956 Mar 1;103(3):295–299. [PMC free article] [PubMed]
  • Soffer RL. Angiotensin-converting enzyme and the regulation of vasoactive peptides. Annu Rev Biochem. 1976;45:73–94. [PubMed]
  • Ng KK, Vane JR. Conversion of angiotensin I to angiotensin II. Nature. 1967 Nov 25;216(5117):762–766. [PubMed]
  • Stanley P, Biron P. Pressor response to angiotensin I during cardio-pulmonary bypass. Experientia. 1969 Jan 15;25(1):46–47. [PubMed]
  • Favre L, Vallotton MB, Muller AF. Relationship between plasma concentrations of angiotensin I, angiotensin II and plasma renin activity during cardio-pulmonary bypass in man. Eur J Clin Invest. 1974 Apr;4(2):135–140. [PubMed]
  • Cushman DW, Cheung HS. Concentrations of angiotensin-converting enzyme in tissues of the rat. Biochim Biophys Acta. 1971 Oct;250(1):261–265. [PubMed]
  • Gocke DJ, Gerten J, Sherwood LM, Laragh JH. Physiological and pathological variations of plasma angiotensin II in man. Correlation with renin activity and sodium balance. Circ Res. 1969 May;24(5 Suppl):131–148. [PubMed]
  • Oparil S, Sanders CA, Haber E. In-vivo and in-vitro conversion of angiotensin I to angiotensin II in dog blood. Circ Res. 1970 May;26(5):591–599. [PubMed]
  • Franklin WG, Peach MJ, Gilmore JP. Evidence for the renal conversion of angiotensin I in the dog. Circ Res. 1970 Sep;27(3):321–324. [PubMed]
  • Aiken JW, Vane JR. Inhibition of converting enzyme of the renin-angiotensin system in kidneys and hindlegs of dogs. Circ Res. 1972 Mar;30(3):263–273. [PubMed]
  • DiSalvo J, Montefusco CB. Conversion of angiotensin I to angiotensin II in the canine mesenteric circulation. Am J Physiol. 1971 Dec;221(6):1576–1579. [PubMed]
  • Collier JG, Robinson BF. Comparison of effects of locally infused angiotensin I and II on hand veins and forearm arteries in man: evidence for converting enzyme activity in limb vessels. Clin Sci Mol Med. 1974 Aug;47(2):189–192. [PubMed]
  • Lanzillo JJ, Fanburg BL. Angiotensin I converting enzyme from human plasma. Biochemistry. 1977 Dec 13;16(25):5491–5495. [PubMed]
  • Ryan JW, Ryan US, Schultz DR, Whitaker C, Chung A. Subcellular localization of pulmonary antiotensin-converting enzyme (kininase II). Biochem J. 1975 Feb;146(2):497–499. [PMC free article] [PubMed]
  • Caldwell PR, Seegal BC, Hsu KC, Das M, Soffer RL. Angiotensin-converting enzyme: vascular endothelial localization. Science. 1976 Mar 12;191(4231):1050–1051. [PubMed]
  • Ferreira SH, Vane JR. The disappearance of bradykinin and eledoisin in the circulation and vascular beds of the cat. Br J Pharmacol Chemother. 1967 Jun;30(2):417–424. [PMC free article] [PubMed]
  • Ng KK, Vane JR. Fate of angiotensin I in the circulation. Nature. 1968 Apr 13;218(5137):144–150. [PubMed]
  • Bakhle YS. Conversion of angiotensin I to angiotensin II by cell-free extracts of dog lung. Nature. 1968 Nov 30;220(5170):919–921. [PubMed]
  • FERREIRA SH. A BRADYKININ-POTENTIATING FACTOR (BPF) PRESENT IN THE VENOM OF BOTHROPS JARARCA. Br J Pharmacol Chemother. 1965 Feb;24:163–169. [PMC free article] [PubMed]
  • Stewart JM, Ferreira SH, Greene LJ. Bradykinin potentiating peptide PCA-Lys-Trp-Ala-Pro. An inhibitor of the pulmonary inactivation of bradykinin and conversion of angiotensin I to II. Biochem Pharmacol. 1971 Jul;20(7):1557–1567. [PubMed]
  • Ondetti MA, Williams NJ, Sabo EF, Pluscec J, Weaver ER, Kocy O. Angiotensin-converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis. Biochemistry. 1971 Oct 26;10(22):4033–4039. [PubMed]
  • Kato H, Suzuki T. Bradykinin-potentiating peptides from the venom of Agkistrodon halys blomhoffi. Isolation of five bradykinin potentiators and the amino acid sequences of two of them, potentiators B and C. Biochemistry. 1971 Mar 16;10(6):972–980. [PubMed]
  • Soffer RL, Reza R, Caldwell PR. Angiotensin-converting enzyme from rabbit pulmonary particles. Proc Natl Acad Sci U S A. 1974 May;71(5):1720–1724. [PMC free article] [PubMed]
  • Dorer FE, Kahn JR, Lentz KE, Levine M, Skeggs LT. Hydrolysis of bradykinin by angiotensin-converting enzyme. Circ Res. 1974 Jun;34(6):824–827. [PubMed]
  • Molteni A, Zakheim RM, Mullis KB, Mattioli L. The effect of chronic alveolar hypoxia on lung and serum angiotensin I converting enzyme activity. Proc Soc Exp Biol Med. 1974 Oct;147(1):263–265. [PubMed]
  • Fanburg BL, Glazier JB. Conversion of angiotensin 1 to angiotensin 2 in the isolated perfused dog lung. J Appl Physiol. 1973 Sep;35(3):325–331. [PubMed]
  • Leuenberger PJ, Stalcup SA, Mellins RB, Greenbaum LM, Turino GM. Decrease in angiotensin I conversion by acute hypoxia in dogs. Proc Soc Exp Biol Med. 1978 Sep;158(4):586–589. [PubMed]
  • Milledge JS, Catley DM. Renin, aldosterone, and converting enzyme during exercise and acute hypoxia in humans. J Appl Physiol Respir Environ Exerc Physiol. 1982 Feb;52(2):320–323. [PubMed]
  • Oparil S, Low J, Koerner TJ. Altered angiotensin I conversion in pulmonary disease. Clin Sci Mol Med. 1976 Dec;51(6):537–543. [PubMed]
  • Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med. 1975 Sep;59(3):365–372. [PubMed]
  • Mue S, Takahashi M, Ohmi T, Shibahara S, Yamauchi K, Fujimoto S, Okayama H, Takishima T. Serum angiotensin converting enzyme level in bronchial asthma. Ann Allergy. 1978 Jan;40(1):51–57. [PubMed]
  • Conroy JM, Hartley JL, Soffer RL. Canine pulmonary angiotensin-converting enzyme. Physicochemical, catalytic and immunological properties. Biochim Biophys Acta. 1978 Jun 9;524(2):403–412. [PubMed]
  • Das M, Soffer RL. Pulmonary angiotensin-converting enzyme. Structural and catalytic properties. J Biol Chem. 1975 Sep 10;250(17):6762–6768. [PubMed]
  • Friedland J, Silverstein E. Similarity in some properties of serum angiotensin converting enzyme from sarcoidosis patients and normal subjects. Biochem Med. 1976 Apr;15(2):178–185. [PubMed]
  • Cushman DW, Cheung HS. Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem Pharmacol. 1971 Jul;20(7):1637–1648. [PubMed]
  • Chiknas SG. A liquid chromatography-assisted assay for angiotensin-converting enzyme (peptidyl dipeptidase) in serum. Clin Chem. 1979 Jul;25(7):1259–1262. [PubMed]
  • Hayakari M, Kondo Y, Izumi H. A rapid and simple spectrophotometric assay of angiotensin-converting enzyme. Anal Biochem. 1978 Feb;84(2):361–369. [PubMed]
  • Hurst PL, Lovell-Smith CJ. Optimized assay for serum angiotensin-converting enzyme activity. Clin Chem. 1981 Dec;27(12):2048–2052. [PubMed]
  • Friedland J, Silverstein E. A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol. 1976 Aug;66(2):416–424. [PubMed]
  • Friedland J, Silverstein E. Sensitive fluorimetric assay for serum angiotensin-converting enzyme with the natural substrate angiotensin I. Am J Clin Pathol. 1977 Aug;68(2):225–228. [PubMed]
  • Dorer FE, Skeggs LT, Kahn JR, Lentz KE, Levine M. Angiotensin converting enzyme: method of assay and partial purification. Anal Biochem. 1970 Jan;33(1):102–113. [PubMed]
  • Russo FS, Persson AV, Wilson IB. A fluorogenic substrate for angiotensin-converting enzyme in plasma. Clin Chem. 1978 Sep;24(9):1539–1542. [PubMed]
  • Carmel A, Ehrlich-Rogozinsky S, Yaron A. A fluorimetric assay for angiotensin-I converting enzyme in human serum. Clin Chim Acta. 1979 Apr 16;93(2):215–220. [PubMed]
  • Kasahara Y, Ashihara Y. Colorimetry of angiotensin-I converting enzyme activity in serum. Clin Chem. 1981 Nov;27(11):1922–1925. [PubMed]
  • Rohrbach MS. [Glycine-1-14C]hippuryl-L-histidyl-L-leucine: a substrate for the radiochemical assay of angiotensin converting enzyme. Anal Biochem. 1978 Jan;84(1):272–276. [PubMed]
  • Mitchell DN, Scadding JG. Sarcoidosis. Am Rev Respir Dis. 1974 Dec;110(6):774–802. [PubMed]
  • James DG, Neville E, Siltzbach LE. A worldwide review of sarcoidosis. Ann N Y Acad Sci. 1976;278:321–334. [PubMed]
  • Massaro D, Handler AE, Katz S, Young RC., Jr Excretion of hydroxyproline in patients with sarcoidosis. Am Rev Respir Dis. 1966 Jun;93(6):929–933. [PubMed]
  • James DG, Turiaf J, Hosoda Y, Williams WJ, Israel HL, Douglas AC, Siltzbach LE. Description of sarcoidosis: Report of the Subcommittee on Classification and Definition. Ann N Y Acad Sci. 1976;278:742–742. [PubMed]
  • Studdy PR, Bird R, Neville E, James DG. Biochemical findings in sarcoidosis. J Clin Pathol. 1980 Jun;33(6):528–533. [PMC free article] [PubMed]
  • Pascual RS, Gee JB, Finch SC. Usefulness of serum lysozyme measurement in diagnosis and evaluation of sarcoidosis. N Engl J Med. 1973 Nov 15;289(20):1074–1076. [PubMed]
  • Werb Z, Gordon S. Secretion of a specific collagenase by stimulated macrophages. J Exp Med. 1975 Aug 1;142(2):346–360. [PMC free article] [PubMed]
  • Silverstein E, Lockerman Z, Friedland J. Serum and lymph-node collagenase in sarcoidosis. Comparison with angiotensin-converting enzyme. Am J Clin Pathol. 1978 Sep;70(3):348–351. [PubMed]
  • Silverstein E, Friedland J, Lyons HA, Gourin A. Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis: clinical and possible pathogenic significance. Ann N Y Acad Sci. 1976;278:498–513. [PubMed]
  • Silverstein E, Friedland J, Lyons HA, Gourin A. Markedly elevated angiotensin converting enzyme in lymph nodes containing non-necrotizing granulomas in sarcoidosis. Proc Natl Acad Sci U S A. 1976 Jun;73(6):2137–2141. [PMC free article] [PubMed]
  • Ashutosh K, Keighley JF. Diagnostic value of serum angiotensin converting enzyme activity in lung diseases. Thorax. 1976 Oct;31(5):552–557. [PMC free article] [PubMed]
  • Fanburg BL, Schoenberger MD, Bachus B, Snider GL. Elevated serum angiotensin I converting enzyme in sarcoidosis. Am Rev Respir Dis. 1976 Sep;114(3):525–528. [PubMed]
  • Silverstein E, Friedland J, Kitt M, Lyons HA. Increased serum angiotensin converting enzyme activity in sarcoidosis. Isr J Med Sci. 1977 Oct;13(10):995–1000. [PubMed]
  • Turton CW, Grundy E, Firth G, Mitchell D, Rigden BG, Turner-Warwick M. Value of measuring serum angiotensin I converting enzyme and serum lysozyme in the management of sarcoidosis. Thorax. 1979 Feb;34(1):57–62. [PMC free article] [PubMed]
  • Rømer FK. Angiotensin-converting enzyme in sarcoidosis. Acta Med Scand. 1979;206(1-2):27–30. [PubMed]
  • Grönhagen-Riska C. Angiotensin-converting enzyme. I. Activity and correlation with serum lysozyme in sarcoidosis, other chest or lymph node diseases and healthy persons. Scand J Respir Dis. 1979 Apr;60(2):83–93. [PubMed]
  • Shultz T, Miller WC, Bedrossian CW. Clinical application of measurement of angiotensin-converting enzyme level. JAMA. 1979 Aug 3;242(5):439–441. [PubMed]
  • Zorn SK, Stevens CA, Schachter EN, Gee JB. The angiotensin converting enzyme in pulmonary sarcoidosis and the relative diagnostic value of serum lysozyme. Lung. 1980;157(2):87–94. [PubMed]
  • James EM, Williams WJ. Fine structure and histochemistry of epithelioid cells in sarcoidosis. Thorax. 1974 Jan;29(1):115–120. [PMC free article] [PubMed]
  • Friedland J, Setton C, Silverstein E. Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture. Science. 1977 Jul 1;197(4298):64–65. [PubMed]
  • Friedland J, Setton C, Silverstein E. Induction of angiotensin converting enzyme in human monocytes in culture. Biochem Biophys Res Commun. 1978 Aug 14;83(3):843–849. [PubMed]
  • Rodriguez GE, Shin BC, Abernathy RS, Kendig EL., Jr Serum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis. J Pediatr. 1981 Jul;99(1):68–72. [PubMed]
  • Lieberman J, Sastre A. Serum angiotensin-converting enzyme: elevations in diabetes mellitus. Ann Intern Med. 1980 Dec;93(6):825–826. [PubMed]
  • Borowsky SA, Lieberman J, Strome S, Sastre A. Elevation of serum angiotensin-converting enzyme level. Occurrence in alcoholic liver disease. Arch Intern Med. 1982 May;142(5):893–895. [PubMed]
  • Lieberman J, Nosal A, Schlessner A, Sastre-Foken A. Serum angiotensin-converting enzyme for diagnosis and therapeutic evaluation of sarcoidosis. Am Rev Respir Dis. 1979 Aug;120(2):329–335. [PubMed]
  • Yotsumoto H, Imai Y, Kuzuya N, Uchimura H, Matsuzaki F. Increased levels of serum angiotensin-converting enzyme activity in hyperthyroidism. Ann Intern Med. 1982 Mar;96(3):326–328. [PubMed]
  • Silverstein E, Friedland J, Lyons HA. Serum angiotensin converting enzyme in sarcoidosis: clinical significance. Isr J Med Sci. 1977 Oct;13(10):1001–1006. [PubMed]
  • Selroos O, Grönhagen-Riska C. Angiotensin converting enzyme. III. Changes in serum level as an indicator of disease activity in untreated sarcoidosis. Scand J Respir Dis. 1979 Dec;60(6):328–336. [PubMed]
  • DeRemee RA, Rohrbach MS. Serum angiotensin-converting enzyme activity in evaluating the clinical course of sarcoidosis. Ann Intern Med. 1980 Mar;92(3):361–365. [PubMed]
  • Baur X, Fruhmann G, Dahlheim H. Follow-up on angiotensin-converting enzyme in serum of patients with sarcoidosis. Respiration. 1981;41(2):133–138. [PubMed]
  • NIH conference. Pulmonary sarcoidosis: a disease characterized and perpetuated by activated lung T-lymphocytes. Ann Intern Med. 1981 Jan;94(1):73–94. [PubMed]
  • Atlas SA, Case DB. Renin in essential hypertension. Clin Endocrinol Metab. 1981 Nov;10(3):537–575. [PubMed]
  • Case DB, Wallace JM, Keim HJ, Weber MA, Sealey JE, Laragh JH. Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme. N Engl J Med. 1977 Mar 24;296(12):641–646. [PubMed]
  • Ondetti MA, Rubin B, Cushman DW. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science. 1977 Apr 22;196(4288):441–444. [PubMed]
  • Cushman DW, Cheung HS, Sabo EF, Ondetti MA. Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry. 1977 Dec 13;16(25):5484–5491. [PubMed]
  • Gavras H, Brunner HR, Turini GA, Kershaw GR, Tifft CP, Cuttelod S, Gavras I, Vukovich RA, McKinstry DN. Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. N Engl J Med. 1978 May 4;298(18):991–995. [PubMed]
  • MacGregor GA, Markandu ND, Roulston JE, Jones JC. Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme. Br Med J. 1979 Nov 3;2(6198):1106–1109. [PMC free article] [PubMed]
  • Roulston JE, MacGregor GA. The measurement of angiotensin-converting enzyme in subjects receiving captopril. N Engl J Med. 1980 Aug 14;303(7):397–397. [PubMed]
  • Kamoun PP, Bardet JI, Di Giulio S, Grunfeld JP. Measurements of angiotensin converting enzyme in captopril-treated patients. Clin Chim Acta. 1982 Feb 5;118(2-3):333–336. [PubMed]
  • Baggio B, Favaro S, Cantaro S, Bertazzo L, Frunzio A, Borsatti A. Increased urine angiotensin I converting enzyme activity in patients with upper urinary tract infection. Clin Chim Acta. 1981 Jan 22;109(2):211–218. [PubMed]
  • Lieberman J, Beutler E. Elevation of serum angiotensin-converting enzyme in Gaucher's disease. N Engl J Med. 1976 Jun 24;294(26):1442–1444. [PubMed]
  • Dobuler KJ, Catravas JD, Gillis CN. Early detection of oxygen-induced lung injury in conscious rabbits. Reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydroxytryptamine. Am Rev Respir Dis. 1982 Sep;126(3):534–539. [PubMed]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Group

Formats: