Triiodothyronine increases serum angiotensin converting enzyme

To determine whether elevated thyroid hormone is responsible for increased serum angiotensin converting enzyme in hyperthyroidism, 5 to 40 micrograms of 3,5,3'-triiodo-L-thyronine was administered orally and subcutaneously to female Swiss-Webster mice. Serum angiotensin converting enzyme was significantly increased in all animals given triiodothyronine compared to controls. Lung and kidney enzymes were moderately reduced in specific activity but unchanged in total activity due to increase in size of these organs. The results indicate that in hyperthyroidism, elevated thyroid hormone per se rather than the disease of the thyroid is responsible for elevated serum angiotensin converting enzyme.     

Serial estimation of serum angiotensin converting enzyme activity during and after pregnancy in a woman with sarcoidosis.

Serum angiotensin converting enzyme activities were estimated during pregnancy and the puerperium in a woman with sarcoidosis and a series of normal women. In the patient with sarcoidosis angiotensin converting enzyme activity was raised during pregnancy, particularly at 21 weeks'' gestation, yet she remained well with no symptoms to suggest relapse of sarcoidosis. Serum angiotensin converting enzyme activity may not be of value in monitoring sarcoidosis activity during pregnancy.     

Increased concentration of angiotensin I converting enzyme in the alveolar fluid of patients with sarcoidosis

Angiotensin converting enzyme (ACE) was assayed both in serum (SACE) and in bronchoalveolar fluid lavage (LACE) in 14 healthy controls and in 45 patients with sarcoidosis with mediastinal and pulmonary involvement. Concentration of SACE was 4466 +/- 2202 U x 100 ml-1 (mean +/- SD) in sarcoidosis and 2470 +/- 547 U x 100 ml-1 (chi +/- SD) in sarcoidosis and 2470 +/- 547 U . 100 ml-1 in controls. Concentrations of LACE were 65.2 +/- 48.4 U . 100 ml-1 and 21.1 +/- 14.7 U . 100 ml-1 respectively in sarcoidosis and in controls. These results are in favor of an intraalveolar secretion of ACE in sarcoidosis. LACE could be a better criterium than SACE for the evaluation of the pulmonary activity of sarcoidosis.     

The angiotensin I converting enzyme.

The angiotensin I converting enzyme (kininase II; peptidyl dipeptidase; EC3.4.15.1) has a dual function: it converts angiotensin I to angiotensin II and it inactivates bradykinin. Lung, kidney, guinea pig plasma and testicles are among the richest sources of the enzyme. Vascular endothelial cells and bursh borders of renal proximal tubular cells contain high concentrations of the enzyme. The availability of synthetic peptide inhibitors was a great help in establishing the function of converting enzyme in normal and pathological conditions.     

Circadian rhythm of the angiotensin converting enzyme (ACE) activity in serum of healthy adult subjects

Angiotensin converting enzyme (ACE) activity was measured in the peripheral serum of 10 healthy, diurnally-active and nocturnally-resting adult subjects (5 women and 5 men). Blood was drawn serially at 4-h intervals throughout a 24-h cycle with the subjects hospitalized and synchronized. They were not kept in recumbency. Data were evaluated by conventional statistical analysis and by single- and population mean- cosinor procedures. A low-amplitude circadian rhythm was statistically validated for the group. Acrophase was located in the afternoon, at about 1630. The recognition that ACE activity oscillates physiologically in the peripheral blood according to a circadian rhythm may serve to amplify the clinical use of ACE measurements.     

Species differences in the angiotensin converting enzyme activity of mammalian serum

Angiotensin converting enzyme (ACE; EC 3. 4. 15. 1) activities were compared in the serum of various mammals. Cattle, human, monkey, and swine serum showed enzyme levels from 3.7 to 67 mU/ml. Relatively high enzyme activity was observed in rodents, the rat (Wistar) and mouse (BALB/c) showing levels of 93 +/- 7 and 1052 +/- 165 mU/ml, respectively. Among the mammalian sera examined, that of the guinea pig contained the highest ACE level, 2262 +/- 574 mU/ml. No age-related difference in enzyme activity was observed in 10-day-old to 1-year-old guinea pigs.     

Low molecular weight angiotensin I converting enzyme from rat lung.

A low molecular weight angiotensin I converting enzyme (light angiotensin enzyme) was isolated from a homogenate of rat lung subjected to dialysis against sodium acetate at pH 4.8. This enzyme has a molecular weight of 84 000 on Sephadex G-200 and a molecular weight of 91 000 on SDS-poly-acrylamide gel as compared with a molecular weight of 139 000 for angiotensin I converting enzyme on SDS-polyacrylamide. Light angiotensin enzyme was activated by NaCl and inhibited by EDTA, angiotensin II, and bradykinin potentiating factor nonapeptide. Light angiotensin enzyme cross-reacted with antibody prepared against angiotensin I converting enzyme and stained with periodic acid-Schiff reagent as a glycoprotein. The evidence suggests that light angiotensin enzyme is a fragment of the higher molecular weight enzyme.     

Isolation and characterization of angiotensin converting enzyme from human kidney

Angiotensin converting enzyme [EC 3.4.15.1] was solubilized from the membrane fraction of human kidney cortex using trypsin and purified to homogeneity by DEAE-cellulose, hydroxylapatite and DEAE-Sephadex A-50 column chromatographies, preparative isoelectric focusing, and Sephadex G-200 gel filtration. The final recovery of the enzyme was 13.9%. The molecular weight of the enzyme was estimated to be 199,000 by a sedimentation equilibrium method. A value of 170,000 was obtained for the reduced and denatured enzyme by dodecylsulfate-polyacrylamide gel electrophoresis. The enzyme was a glycoprotein consisting of a single polypeptide chain with an isoelectric point of 5.10. Neutral sugar accounted for 13% per weight of the enzyme. The purified enzyme had a specific activity of 96.9 mumol/min/mg protein for hippurylhistidylleucine. The Km value, Kcat value and hydrolytic coefficient (Kcat/Km) of the enzyme for hippurylhistidylleucine were 2.0 mM, 545 s-1 and 273 mM-1 . s-1, respectively. Rabbit antibody against the human kidney converting enzyme inhibited the activities of the enzymes from human lung and serum as equally as that from human kidney, but not those from sheep, dog, or rat sera. The human kidney and lung converting enzymes were immunologically identical on double immunodiffusion analysis.     

Purification and study of the physicochemical properties of angiotensin converting enzyme from the human liver

Angiotensin-converting enzyme (ACE) from human liver was first purified 9000-fold by chromatofocusing with 22% yield. The enzyme had a specific activity of 10 U/mg. The enzyme molecular weight was 150000, as determined by electrophoresis in a 7.5% polyacrylamide gel. The enzyme pI determined by chromatofocusing was 4.2-4.3. KM of human liver ACE, measured using hippuryl-L-histidyl-L-leucine and N-benzyloxycarbonyl-L-phenylalanyl-L-histidyl-L-leucine as substrates, was 5 mM and 0.1 mM, respectively. Human liver ACE was inhibited by SQ 20881 with IC50 equal to 1.8 X 10(-8) M.     

Purification of bovine angiotensin converting enzyme

A change has been made in the commonly used lisinopril affinity gel procedure for purifying angiotensin converting enzyme. The new method greatly decreases the time required and greatly increases the yield of pure enzyme. All of the enzyme in various bovine tissues was extracted with 0.5% triton X-100 and applied to the affinity column; 70% was trapped and all of the trapped enzyme was released as the apoenzyme by EDTA. The holoenzyme was recovered by dialysis against zinc containing buffer. The turnover numbers were precisely the same for enzyme from lung, atrium, kidney, striatum and blood. The tissue concentrations of ACE were very different but the final specific activities were the same.     

The history of inhibitors of angiotensin converting enzyme.

This review paper by Sir John Vane, The Nobel Prize Laureate for the first time reveals the insides of discovery of inhibitors of angiotensin converting enzyme (ACE-1), presently known as important drugs for the treatment of hypertension, congestive heart failure and coronary artery disease.     

Induction of angiotensin converting enzyme in human monocytes in culture.

Angiotensin converting enzyme (E.C.3.4.15.1, peptidyl dipeptidase) in circulating human monocytes rose from undetectable or minimal levels $\text{in}\text{vivo}$ to as high as 35.5 nmol/min·mgprotein (>300-fold increase) after 6 or 7 days in culture. Enzyme induction was enhanced by autologous serum and exposure for two days to 0.45 μM dexamethasone. Potent inhibition of enzyme induction by 370 μg/ml of actinomycin D and 1 μM cycloheximide suggested that new messenger RNA and enzyme biosynthesis are involved in the induction. Human monocyte and lung enzyme were similar with respect to EDTA inhibition, CoCl₂ activation and inhibition by an antienzyme antiserum. Human lymphocytes had minimal or undetectable enzyme which was not induced after 4 days in culture.     

A continuous spectrophotometric assay for angiotensin converting enzyme.

Furanacryloyl tripeptides conforming to the known substrate specificity of the angiotensin converting enzyme (dipeptidyl carboxypeptidase, EC 3.4.15.1) have been employed to provide a continuous spectrophotometric assay for this peptidase in the visible region. The assay is based on a blue shift of the absorption spectrum that occurs upon hydrolysis of the substrate to produce a furanacryloyl-blocked amino acid and a dipeptide. Of the various furanacryloyl tripeptides tested, furanacryloyl-l-phenylalanylglyeylglycine exhibits the most suitable characteristics for routine assays of angiotensin converting enzyme.     

New potent inhibitors of angiotensin converting enzyme

Using an earlier model of the favoured orientation of binding functions of angiotensin converting enzyme (ACE) inhibitors, it has been possible to postulate a new, 7,6-bicyclic system, based on hexahydropyridazine, which might be expected to have high potency. Some members of this system which have been synthesised have been shown to be very active ACE inhibitors, in vitro and in vivo.