Increased Serum Angiotensin-converting Enzyme Activity Research Articles

Investigation of The Effect of Aminoglycosides on Angiotensin Converting Enzyme (ACE)

Objective: The research attention to nephrotoxicity from antibiotics (as aminoglycosides), non-steroidal anti-inflammatory drugs, and antifungals, angiotensin-converting enzyme (ACE) inhibitors. Several drugs have resulted in produce an adverse effect on kidneys. Angiotensin-converting enzyme (ACE) is a component of the renin-angiotensin system (RAS), which leads to the conversion of angiotensin-I to angiotensin-II in vascular tissues. The present study aimed to determine serum ACE activity in rats with an aminoglycosine.
 
 Material-Method: In this study, two different groups formed, the control group (10 rats/Wistar-albino female) and the experimental group (30 rats/Wistar-albino female) administered aminoglycosine (Amikacin). Aminoglycosine was administered intraperitoneally to the experimental group at a single dose of 15 mg/kg body weight at the same time each day for 14 days. The control group implemented physiological water instead of aminoglycosine at the same rate. 
 
 Result: When the groups compared according to the statistic results, it is observed that there was a significant increase in the experimental group according to the control group (p˂0.001).
 
 Conclusion: As a result, it was determined that aminoglycosin administered increased serum ACE activity and it was concluded that it may be useful to investigate the possibilities to evaluate it as a risk factor and indicator in the development of hypertension

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients.Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed.Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05).Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

Angiotensin converting enzyme activity in alopecia areata.

Background. Alopecia areata (AA) is a chronic inflammatory disease of the hair follicle. The exact pathogenesis of AA remains unknown, although recent studies support a T-cell mediated autoimmune process. On the other hand, some studies have proposed that the renin-angiotensin-aldosterone system (RAAS) may play a role in autoimmunity. Therefore, we assessed serum activity of angiotensin converting enzyme (ACE), a component of this system, in AA. Methods. ACE activity was measured in the sera of 19 patients with AA and 16 healthy control subjects. In addition, the relationship between severity and duration of the disease and ACE activity was evaluated. Results. Serum ACE activity was higher in the patient group (55.81 U/L) compared to the control group (46.41 U/L), but the difference was not statistically significant (P = 0.085). Also, there was no correlation between ACE activity and severity (P = 0.13) and duration of disease (P = 0.25) in the patient group. Conclusion. The increased serum ACE activity found in this study may demonstrate local involvement of the RAAS in the pathogenesis of AA. Assessment of ACE in a study with a larger sample size as well as in tissue samples is recommended in order to further evaluate the possible role of RAAS in AA.

The CC genotype of the angiotensin II type I receptor gene independently associates with acute myocardial infarction in a Tunisian population

Acute myocardial infarction (AMI) is a multifactorial disease influenced by environmental and genetic factors. The aim of this study was to assess the association of angiotensin II type 1 receptor (ATR1) gene polymorphisms with AMI as well as to evaluate the role of serum angiotensin-converting enzyme (ACE) activity and that of cardiac troponin I (cTnI) in Tunisian AMI patients. One hundred and eighteen AMI patients were compared to 150 healthy controls. ATR1 genotypes were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The ATR1 A1166C polymorphism was significantly associated with AMI (p = 0.024). CC genotype and C allele frequencies were associated with increased AMI risk [CC vs. AC and AA: OR = 2.06; p = 0.045; 95 % CI (1.02-4.18); C vs. A: OR = 1.68; p = 0.004; 95 % CI (1.17-2.41)]. By multivariate logistic regression analysis, CC genotype, hypertension, diabetes, serum ACE activity and peak-cTnI were significant independent predictors of AMI. Increased serum ACE activity and cTnI peak levels were associated with the CC genotype in AMI patients. In conclusion, the ATR1 A1166C polymorphism is associated with AMI and the CC genotype associated with increased ACE activity and cTnI levels appear to predispose for AMI risk.

Terephthalic acid occupational exposure and its effect on organ functions in fiber workers

Objectives: To investigate the exposure to terephthalic acid (TPA), and to evaluate it's effects on organ function including the potential risk factors for uroliths and bladder tumor to TPA. Methods: Exposure–response modeling was carried out in a cohort of 141 TPA exposure workers and three subgroups were classified according to their urine TPA concentration. The control group consisted of 77 workers with no exposure to TPA dust. The inhalatory exposure of the application workers was estimated from biological monitoring data. Urine and blood samples were collected from all workers before and after work shift to monitor variables of liver, kidney, and lung. Haematological variables and serum biochemistry were valued, pulmonary functions were tested, and ion changes in both serum and urine were measured. Results: Increased urinary excretion of TPA (0–5 mmol/mol Cr after the shift) reflected occupational workers TPA exposure. We also observed the exposure–response relations for the intensity of TPA exposure and the urine variables. Increased serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) but within normal range is not increased. The slightly increased serum angiotensin-converting enzyme activity (SACE) was considered to be related to particulate of airborne TPA dust inhalation. No difference between referents and workers exposed to TPA was found for haematological variables. Conclusions: No clinical organ dysfunctions were found in this investigation working with TPA. However, special precautions are still necessarily taken to avoid excessive or prolonged contact.

Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat.

The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, electrolyte balance and renal function in normal human pregnancy. The present study was designed to assess various components of the RAS and renal function during pregnancy and immediately after pregnancy in the streptozotocin (STZ)-diabetic rat. Pregnant Wistar rats were allocated to three groups: I-control, non-diabetic rats (n=24), II-STZ-diabetic rats (STZ 55 mg/kg body weight, i.v. on day 10 of pregnancy, n=24), III-diabetic rats, as above, treated with insulin (4 units/day, s.c. n=21). On days 17-18 of pregnancy, or within 24 hours after delivery, the rats were sacrificed and the various components of the RAS were determined. Urinary protein excretion (UP) and creatinine clearance(CCr) were greater in group II, four days after STZ, than in group I (UP: I-7.6+/-2.8, II-18.6+/-6.3 mg/24-hour, p<0.001, CCr: I-1.04+/-0.33, II-2.38+/-0.7 ml/minute, p<0.001). Mean (+/-SD) serum angiotensin-converting enzyme (ACE) activity and plasma angiotensin II(Ang II) levels at days 17-18 of pregnancy were greater in the untreated diabetic rats than in control pregnant rats (ACE: 163+/-18 vs. 111+/-21 nmol/ml/minute, p<0.001, Ang II: 115+/-45 vs. 43+/-10 pg/ml, p<0.005). Postpartum serum ACE activity and plasma Ang II levels were greater in group II (ACE: I-123+/-14, II-142+/-24, III-108+/-21 nmol/ml/minute, p<0.01, Ang II: I-56+/-38, II-148+/-62, III-38+/-17 pg/mI, p<0.001). ACE activity in the lung was greater, whereas the activity in the renal cortex was less, in group II than in group I. Kidney weight in untreated diabetic rats was greater than in the other two groups. Increased serum ACE activity during pregnancy and postpartum in the untreated diabetic rat is associated with enhanced serum Ang II levels, which may contribute to increased protein excretion and renal hypertrophy.

Plasma angiotensin II, renin activity and serum angiotensin-converting enzyme activity in non-insulin dependent diabetes mellitus patients with diabetic nephropathy.

The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy. Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65+/-0.10 ng/ml/hr) was significantly reduced than the controls (1.28+/-0.37 ng/ml/hr) (P<0.001), the diabetic group with microalbuminuria (1.08+/-0.48 ng/ml/hr) (P<0.05) and normoalbuminuric patients (1.56+/-0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36+/-1.49 pg/ml vs 14.87+/-3.48 pg/ml respectively, p<0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99+/-5.88 pg/ml) than non-complicated diabetics (p<0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9+/-28.3 nmol/min/ml, microalbuminuric NIDDM 127.9+/-31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0+/-29.3 nmol/min/ml) when compared to the normal control group (76.3+/-16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy. No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.

ACE insertion/deletion genotype affects bradykinin metabolism.

A deletion allele of the angiotensin-converting enzyme (ACE) gene has been associated with increased serum ACE activity, enhanced conversion of angiotensin (Ang) I to Ang II, and cardiovascular morbidity. This study tested the hypothesis that the ACE deletion allele is also associated with enhanced degradation of bradykinin, a vasoprotective peptide. Metabolism of synthetic bradykinin was measured in sera obtained from subjects who were homozygous for either the ACE deletion (n=12) or insertion (n=8) allele and who had participated in an Ang I-infusion protocol. ACE levels tended to be increased in subjects who were DD compared with those who were II [41.2 (95% CI, 27.9, 54.3) vs. 28.0 IU/L (20.0, 35.9); t=-1.6; p=0.1 18]. During Ang I infusion, plasma Ang II concentrations were increased in DD compared with II subjects (F =4.4; p=0.052). In contrast, the half-life of bradykinin was significantly decreased in sera obtained from ACE DD compared with II subjects [26.3 s (17.8, 34.6 s) vs. 42.1 s (24.4, 59.9 s); t=-2.4; p=0.029]. Moreover, there were significant inverse relations between the half-life of bradykinin and serum ACE activity (p < 0.001) and between the half-life of bradykinin and the conversion of Ang I to Ang II (p=0.026). This study confirms that ACE genotype determines bradykinin degradation and suggests another mechanism whereby the ACE D allele could be associated with deleterious cardiovascular effects.

Monocrotaline-induced cardiopulmonary damage in rats: amelioration by the angiotensin-converting enzyme inhibitor CL242817.

Pulmonary injury induced by the plant alkaloid monocrotaline is partially prevented by the angiotensin-converting enzyme (ACE) inhibitor captopril. CL242817 [(S-[R*,S*])-1-([3-acetylthio]-3-benzoyl-2-methyl-propionyl)- L-proline] is a new orally active ACE inhibitor under evaluation as an antihypertensive agent. To determine whether CL242817 also can modify monocrotaline-induced pulmonary injury, male rats were divided into four groups: control; CL242817 (60 mg/kg/day, po); monocrotaline (2.4 mg/kg/day, po); or monocrotaline plus CL242817, and were sacrificed after 6 weeks of continuous treatment. Rats receiving monocrotaline alone exhibited occlusive medial thickening of the pulmonary arteries, cardiomegaly, and right ventricular hypertrophy. Electron micrographs of monocrotaline-treated lung revealed degeneration of both endothelial and Type I epithelial cells, as well as marked interstitial hypercellularity and fibrosis. Hydroxyproline (collagen) content of monocrotaline-treated lung also increased significantly, confirming the fibrosis observed in the electron micrographs. These structural changes were accompanied by decreased lung ACE and plasminogen activator (PLA) activities, indicative of pulmonary endothelial dysfunction. Concomitant CL242817 treatment ameliorated all anatomic manifestations of monocrotaline injury, particularly the right ventricular hypertrophy, pulmonary arterial occlusion, epithelial degeneration, and interstitial fibrosis. CL242817 also significantly prevented the monocrotaline-induced increase in lung hydroxyproline content. In contrast, concomitant CL242817 did not significantly influence the suppressed lung ACE and PLA activities in monocrotaline-treated rats. CL242817 alone produced retarded weight gain, decreased heart weight relative to body weight, decreased lung hydroxyproline content and ACE activity, and increased serum ACE activity and plasma AII concentration. Thus CL242817 resembles captopril, both in its ability to ameliorate monocrotaline-induced pulmonary injury in rats, and in many of its side effects.

Monocrotaline-induced pulmonary fibrosis in rats: amelioration by captopril and penicillamine.

The purpose of this study was to determine whether Captopril (an angiotensin converting enzyme inhibitor) or D-penicillamine (an inhibitor of collagen crosslinking) can ameliorate pulmonary fibrosis induced by the plant alkaloid monocrotaline. Rats were randomly assigned to one of six treatment groups: (1) control; (2) Captopril, 60 mg/kg/day, p.o.; (3) D-penicillamine, 30 mg/kg/day, p.o.; (4) monocrotaline, 2.4 mg/kg/day, p.o.; (5) monocrotaline plus Captopril, as above; (6) monocrotaline plus penicillamine, as above; and were killed after 6 weeks of continuous drug administration. Monocrotaline-treated rats exhibited several anatomic correlates of pulmonary hypertension, including cardiomegaly, right heart enlargement, and muscularization of the pulmonary arteries and arterioles. These monocrotaline reactions were accompanied by decreased lung activities of angiotensin converting enzyme (ACE) and plasminogen activator (PLA), indicative of endothelial dysfunction; and by increased lung hydroxyproline concentration, indicative of interstitial fibrosis. The presence of interstitial fibrosis was confirmed by electron microscopy. When given concomitantly with monocrotaline, both Captopril and penicillamine partially prevented the cardiomegaly, right heart enlargement, and vascular muscularization. Both agents also diminished the decreased lung PLA activity and increased hydroxyproline concentration observed in monocrotaline-treated animals. Neither modifying agent influenced the monocrotaline-induced decrease in lung ACE activity. Compared with control rats, the rats receiving Captopril alone exhibited decreased heart weight and increased serum ACE activity, and animals receiving penicillamine alone did not differ significantly from control animals for any of the endpoints studied. These data demonstrate that Captopril and penicillamine ameliorate monocrotaline-induced pulmonary fibrosis in rats. Penicillamine, known to inhibit radiation-induced lung injury, thus is shown to be effective in a second model of pulmonary fibrosis. Perhaps more importantly, the hydroxyproline data demonstrate that the ACE inhibitor Captropril exhibits antifibrotic activity in monocrotaline-treated rat lung.

Transcobalamin II: a marker for macrophage/histiocyte proliferation.

Increased blood levels of (apo-)transcobalamin II have been observed in several clinical conditions, but persistent inability to find a common denominator for this plasma protein aberration has hampered its introduction as a clinically useful laboratory parameter. Because several observations suggested a relationship between reticuloendothelial cell activity and transcobalamin II, the finding of an extreme transcobalamin II elevation in a patient with malignant histiocytosis was taken seriously. Of 14 consecutive patients with proliferative histiocytosis (8 malignant, 6 reactive), all revealed marked to extreme elevations of transcobalamin II. Macrophage/histiocyte origin of this protein is supported by a close parallelism to increased serum angiotensin-converting enzyme activity. Comparative pre- and postoperative measurements of transcobalamin II and angiotensin-converting enzyme in four patients with histiocytic proliferation who underwent splenectomy, an intervention that led to immediate reduction of the macrophage/histiocyte cell pool, revealed a parallel and impressive drop of both parameters, further corroborating the histiocytic origin of transcobalamin II. It is suggested that transcobalamin II determination provides useful information on activity and size of the macrophage/histiocyte system, and supplements measurements of the traditional acute phase reactants (e.g., C-reactive protein, red blood cell sedimentation rate).

Tissue distribution of angiotensin converting enzyme in the rat: effect of captopril treatment.

Effect on different tissues with regard to angiotensin converting enzyme during captopril treatment in the rat was studied. Male Wistar-Kyoto rats (n = 9) were treated during four weeks with captopril dissolved into the drinking water at the dose 30 mg/kg/day. Control rats (n = 9) had water only. Serum angiotensin converting enzyme (ACE) activity increased three-fold during captopril treatment, and ACE of purified pulmonary plasma membranes increased about 64% (P less than 0.001) compared to untreated rats. ACE activity of membrane fractions of other tissues studied i.e. testicles, epididymes, kidneys, and small intestine brush border did not increase similarly during captopril treatment. The highest amounts of ACE was demonstrated in epididymes, but captopril did not produce increased amounts of ACE in the epididymes. The main source of increased serum ACE activity during captopril treatment appeared to be in the pulmonary tissue.

Serum Angiotensin Converting Enzyme Activity in Patients With Histoplasmosis

The association between increased serum angiotensin converting enzyme (ACE) activity and active sarcoidosis is well documented. During a recent outbreak of acute histoplasmosis, a disease that shares many of the clinical and roentgenographic features of sarcoidosis, we examined serum ACE activity. Twenty-one (25%) of 86 patients with histoplasmosis had increased serum ACE activity. There were neither roentgenographic nor other substantive clinical differences between the groups of patients with increased and normal ACE values. Therefore, an increase in serum ACE activity must not be assumed to be caused by sarcoidosis unless histoplasmosis had been excluded.