Angiotensin-converting enzyme activity in isolated brain microvessels.

The localization of angiotensin-converting enzyme (kininase II; ACE) in bovine cerebral cortex was studied by mechanically isolating microvessels from surrounding brain parenchyma. ACE specific activity, as assayed by generation of L-histidyl-L-leucine from the synthetic substrate hippuryl-L-histidyl-L-leucine, was enriched approximately 30 times in microvessels compared to homogenates of intact cerebral cortical gray matter. The nonapeptide 9a, SQ20,881), the orally active anti-hypertensive drug, 2-D-methyl-3-mercaptopropanoyl-L-proline (SQ14,225), and the vasoactive peptides bradykinin and angiotensin II inhibited this activity in a dose-dependent fashion. Brain microvessel ACE required chloride for optimal activity, was potentiated by cobalt nitrate, and was inhibited by the chelating agents EDTA and o-phenanthroline. Enzymatic generation of histidyl-leucine also was observed with the naturally occurring decapeptide substrate angiotensin I. In addition, microvessels obtained from bovine cerebellar cortex, hippocampus and corpus striatum, as well as from the cerebral cortex of Sprague-Dawley rats, were enriched in ACE activity. The presence of angiotensin-converting enzyme in brain microvessels suggests that cellular components of the blood-brain barrier may participate in the metabolism of peptide hormones such as angiotensin I and bradykinin within the central nervous system.     

Angiotensin-converting enzyme activity in ovine bronchial vasculature.

Angiotensin-converting enzyme (ACE) plays a major role in the metabolism of bradykinin, angiotensin, and neuropeptides, which are all implicated in inflammatory airway diseases. The activity of ACE, which is localized on the luminal surface of endothelial cells (EC), has been well documented in pulmonary EC; however, few data exist regarding the relative activity of ACE in the airway vasculature. Therefore, we measured ACE activity in cultured EC from the sheep bronchial artery and bronchial mucosa (microvascular) and compared it with pulmonary artery EC. The baseline level of total ACE activity (cellular plus secreted) was significantly greater in bronchial microvascular EC (1.24 +/- 0.24 mU/106 cells) compared with bronchial artery EC (0.59 +/- 0.15 mU/106 cells; P < 0.05) and comparable to pulmonary artery EC (1.12 +/- 0.14 mU/106 cells; P > 0.05). Measured ACE activity secreted into culture medium for each cell type was 64-74% of total activity and did not differ among the three EC types (P = 0.17). Hydrocortisone (10 microg/ml; 48-72 h) treatment resulted in a significant increase in ACE activity in bronchial EC. Likewise, TNF-alpha (0.1 ng/ml) treatment markedly increased ACE activity in all cell lysates (P < 0.05). We confirmed the importance of ACE activity in vivo since, at the highest dose of bradykinin studied (10-8 M), bronchial artery pressure at constant flow showed a greater decrease after captopril treatment (36% before vs. 60% after; P = 0.05). These results demonstrate high ACE expression of the bronchial microvasculature and suggest an important regulatory role for ACE in the metabolism of kinin peptides known to contribute to airway pathology.     

Angiotensin-converting enzyme in Spodoptera littoralis: molecular characterization, expression and activity profile during development

The characterization of the full-length angiotensin-converting enzyme (ACE) cDNA sequence of the lepidopteran Spodoptera littoralis is reported in this study. The predicted open reading frame encodes a 647 amino acids long protein (SlACE) and shows 63.6% identity with the Bombyx mori ACE sequence. A 3D-model, consisting of 26 alpha-helices and three beta-sheets, was predicted for the sequence. SlACE expression was studied in the embryonic, larval and pupal stages of S. littoralis and in different tissues of the last larval stage by reverse-transcribed PCR. This revealed that the gene is expressed throughout the life cycle and especially in brain, gut and fat body tissue of the last stage. These results are in agreement with a role of ACE in the metabolism of neuropeptides and gut hormones. In addition, ACE activity has been studied in more detail during development, making use of a fluorescent assay. High ACE peptidase activity coincides with every transition state, from embryo to larva, from larva to larva and from larva to pupa. A peak value in activity occurs during the early pupal stage. These results indicate the importance of SlACE during metamorphosis and reveal the high correlation of ACE activity with the insect's development, which is regulated by growth and developmental hormones.     

Angiotensin-converting enzyme activity in experimental alcoholic fatty liver of the rat

Angiotensin-converting enzyme (ACE) activity was found increased in serum of patients with chronic alcoholism. We studied this enzymatic activity in serum and liver tissue of rats with alcoholic fatty liver due to prolonged intake of ethanol with a liquid diet, according to De Carli and Lieber. Serum and liver ACE activity did not show any significant increase in rats with alcoholic fatty liver when compared with controls, whereas gamma-glutamyltransferase activity exhibited a striking enhancement in serum and liver. Our data suggest that ACE is not an alcohol-induced enzyme in the experimental rat model.     

Angiotensin-converting enzyme and anorexia nervosa

Angiotensin-converting enzyme (ACE) activity was measured in 10 patients with anorexia nervosa, 6 with hyperthyroid Graves' disease, and 7 with primary hypothyroidism. Patients with anorexia nervosa had a low serum ACE activity (9.8 +/- 2.2 IU/l), as compared to findings in normal subjects (13.4 +/- 3.5 IU/l) (P less than 0.05). Patients with hyperthyroid Graves' disease had high serum ACE activity (23.7 +/- 5.8 IU/l), as compared to levels in normal subjects (P less than 0.01), and patients with primary hypothyroidism tended to have low serum ACE activity (10.1 +/- 1.8 IU/l), compared to the normal subjects (P less than 0.1). Following weight gain (before; 71.3 +/- 10.2% of ideal body weight, after; 88.7 +/- 5.6% of ideal body weight), serum ACE activity in patients with anorexia nervosa reverted to within the normal range (13.8 +/- 3.5 IU/l), and serum T3 concentration was restored to the normal range (before; 0.7 +/- 0.2 ng/ml, after; 1.1 +/- 0.3 ng/ml). In these patients, ACE activity correlated with the per cent of ideal body weight (P less than 0.05). These data suggest that, in underweight subjects with anorexia nervosa, decreased serum ACE activities may relate to emaciation.     

Angiotensin-converting enzyme genotype and physical performance during US Army basic training.

Prior studies have suggested that angiotensin I-converting enzyme (ACE) genotype correlates with superior physical performance in highly selected populations. This study assessed whether such an association exists in a heterogeneous population. Using polymerase chain reaction techniques, we determined the ACE genotypes (insertion/insertion, deletion/insertion, or deletion/deletion) of 62 male and 85 female US Army recruits. Before and after 8 wk of basic training, we determined peak oxygen uptake and performance on the Army Physical Fitness Test (APFT), which includes standardized measures of muscular endurance (sit-ups, push-ups) and a 2-mile run. Subjects of different ACE genotypes had similar peak oxygen uptakes and APFT scores, both before and after training. Subjects with genotype II had higher APFT scores than others, but the differences were not statistically significant. Furthermore, no ACE genotype group had a performance advantage in analyses that adjusted for baseline fitness. We conclude that ACE genotype does not have a strong effect on aerobic power or muscular endurance in healthy, young American adults drawn from an ethnically and geographically diverse population.     

Angiotensin-converting enzyme and cardiovascular disease risk.

The published studies of the association of the angiotensin-converting enzyme (ACE) genotype with cardiovascular disease have used many different diagnostic criteria for cardiovascular disease and have drawn their samples from different patient groups and different populations. This review examines the association of the ACE DD genotype with cardiovascular disease risk in studies grouped by their case criterion, the geographical region of the population samples, and by the cardiovascular risk level of the patient sample. In studies where the underlying odds ratios are determined to be homogeneous, the overall odds ratios for myocardial infarction and coronary artery disease with regard to the ACE DD genotype are estimated using the Mantel-Haenszel method.     

Angiotensin-converting enzyme signalling in human preadipocytes and adipocytes

Angiotensin-converting enzyme (ACE, kininase II) is a plasma membrane zinc metallopeptidase that acts as a key enzyme for the extracellular conversion of vasoactive peptides. Recently, ACE outside-in signalling in endothelial cells has been described. The present study tested the hypothesis that ACE signalling is not restricted to endothelial cells and may act as an additional peptide receptor on human preadipocytes and adipocytes. ACE protein levels were not changed during adipose conversion of human primary preadipocytes. The enzyme was primarily localized to the non-detergent-resistant fraction of the membrane and phosphorylated in non-dividing cells. Antibody arrays of whole cell lysate detected putative ACE-interacting proteins, which all share important roles in cell cycle control and/or apoptosis. These findings suggest that ACE is a versatile molecule, involved both in the regulation of extracellular peptide concentrations and direct intracellular signalling. In human adipose cells ACE may potentially influence exit from the cell cycle, differentiation, and programmed cell death signalling.     

Angiotensin-converting enzyme inhibition reduces neuroblastoma cell growth rate

Because of the known capacity of angiotensin II to serve as a growth factor in multiple tissues, we elected to study the effects of renin-angiotensin system inhibition on the growth of human SH-SY5Y neuroblastoma cells. Cells were treated with captopril (0.05-5 mg/ml), enalapril, or enalaprilat (0.02-5 mg/ml) or saralasin (0.1-0.25 mg/ml). In all cases, statistically significant reductions in cell growth were seen over 5 days of culture. In additional experiments, captopril and enalaprilat significantly decreased thymidine incorporation into DNA in these cells. The administration of angiotensin II in the presence of captopril partially offset these suppressive effects.     

Angiotensin-converting enzyme and metals in untreated essential hypertension

Hpertension is an important health problem throughout the world and a risk factor for many diseases. Angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system, has an important role in the regulation of blood pressure. Zinc (Zn), a trace element with important biological functions, is located in the catalytic site of ACE. Calcium (Ca), magnesium (Mg), sodium (Na), and potassium (K) also appear to be involved in hypertension pathogenesis. In this study, plasma ACE activities and Ca_t, Ca_i, Mg, Na, K, and plasma/erythrocyte Zn levels of 20 untreated patients with essential hypertension and 28 helthy individuals were evaluated. Plasma ACE activities (p<0.05) and erythrocyte Zn concentrations (p<0.001) were significantly higher in patients with essential hypertension than values of the control group. No significant difference was found between plasma Zn concentrations of the groups (p>0.05). Plasma Ca_t (p<0.001) and Mg levels (p<0.05) in essential hypertension were significantly lower than those of controls. Plasma Na, K, and Ca_i levels remained normal in essential hypertension. There are complex associations between metals and arterial pressure. Ca and Mg deficiencies seem to be associated with increased prevalence of hypertension. Increases in erythrocyte Zn may have a future potential use for diagnosis of hypertension.     

Changes in the activity of trout lysosomal enzymes during fasting

Activity of lysosome enzymes (acidic phosphatase, beta-glucosidase, DNAase, RNAase and cathepsin D) is determined for its variation in different organs of rainbow trout during complete fasting. It is shown that the activity of most enzymes of concern almost in all organs except skeletal muscles is on the higher level in trouts fasted for 30 days than in the control ones. With an increase of the fasting term to 60 days the acid phosphatase, DNAase, RNAase activity decreases while the glucosidase and cathepsin D activity in some organs increases. Variations detected in the enzyme profile of the trout lysosomes under fasting are of adaptive character.