Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The heptapeptide angiotensin-(1-7) is a circulating biologically active product of the renin-angiotensin system. In this study, we evaluated the role of the vascular endothelium in the formation of angiotensin-(1-7). Metabolism of 125I-angiotensin I was investigated using confluent cultured bovine and human aortic and umbilical vein endothelial cells. The fetal calf serum-supplemented medium was replaced by serum-free medium containing 0.2% bovine serum albumin. One hour later, this medium was replaced by serum-free medium containing 125I-angiotensin I. After incubation of 125I-angiotensin I for various intervals at 37 degrees C, the medium was collected and analyzed for formed products by high-performance liquid chromatography. Products of angiotensin I metabolism were identified by comparison of their retention times with those of radiolabeled standards. The contribution of proteases released into the medium was evaluated by incubation of 125I-angiotensin I with medium previously incubated for 1 hour with endothelial cells. Incubation of 125I-angiotensin I with bovine and human endothelial cells produced a time-dependent generation of 125I-angiotensin-(1-7) greater than 125I-angiotensin II greater than 125I-angiotensin-(1-4). Generation of angiotensin peptides was not due to the presence of proteases in the medium. When human umbilical endothelial cells were incubated in the presence of the angiotensin converting enzyme inhibitor enalaprilat (1 microM), generation of angiotensin II was undetectable. In contrast, angiotensin-(1-7) production increased by an average of 30%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production of angiotensin-(1-7) by human vascular endothelium. 131 Apr 84

The role of NO-formation induced by accumulated endogenous bradykinin (BK) via local ACE-inhibition with ramiprilat (RT) or by adding BK exogenously was evaluated in cultured bovine aortic endothelial cells (BAEC) and in isolated rat hearts with post-ischaemic reperfusion injuries. Furthermore we used the n-octyl-ester of ramipril (RA-octil) which was shown to have no ACE-inhibitory action. In BAEC, ACE-inhibition by RT (1 x 10(-8)-1 x 10(-6) mol/l) or addition of BK (1 x 10(-8)-1 x 10(-6) mol/l) stimulated the formation of NO and prostacyclin (PGI2) as assessed by endothelial cyclic GMP- and 6-keto-PGF1a formation. Cyclic GMP and PGI2 synthesis was completely suppressed by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 1 x 10(-5) mol/l) and by the B2 kinin receptor antagonist HOE 140 (1 x 10(-7) mol/l). RA-octil (1 x 10(-8)-1 x 10(-4) mol/l) did not affect endothelial cyclic GMP production in BAEC. In isolated working rat hearts subjected to local ischemia with reperfusion both RT (1 x 10(-8) mol/l) and BK (1 x 10(-9) mol/l) reduced the incidence and duration of ventricular fibrillation. In parallel myocardial function (left ventricular pressure, coronary flow) and metabolism (high energy rich phosphates) were improved showing a comparable fingerprint for RT and BK. Addition of L-NNA (1 x 10(-6) mol/l) or HOE 140 (1 x 10(-9) mol/l) abolished these protective effects of RT and BK. As in the BAEC studies RA-octil was without beneficial effects on the isolated ischaemic rat heart. The findings on BAEC show that inhibition of ACE localized on the luminal side of the vascular endothelium results in increased synthesis of NO and prostacyclin by local accumulation of endothelium-derived BK. Similar mechanisms may occur in the ischaemic rat heart leading to cardioprotection.
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PMID:ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts. 133 74

Elevated serum angiotensin I-converting enzyme activity may occur in diabetic subjects. This may signal alteration of vascular endothelium. To study the effect of acute glucose change on serum Angiotensin Converting Enzyme (ACE), we performed an oral glucose tolerance test in 17 obese subjects (7M/10F), (Body Mass Index, (BMI): 31 +/- 1 kg/m2), aged 48 +/- 3 years. We measured serum ACE activity (Lieberman's method), active renin (RIA Pasteur kit), and aldosterone (RIA, Cis-International kit), before and 2 hours after oral glucose intake (75 g), and plasma glucose and insulin every 30 min. After oral glucose tolerance test, subjects were classified as 6 Non Insulin-Dependent Diabetic (NIDD), 8 Glucose intolerant (GI), and 3 NormoGlycaemic (NG) subjects. Active renin did not vary after glucose loading (14 +/- 2 vs 15 +/- 2 pg/ml) nor aldosterone (104 +/- 14 vs 133 +/- 18 pg/ml), while ACE activity rose significantly (229 +/- 25 vs 277 +/- 28 IU/l; p = 0.02). Serum ACE activity were different in the 3 groups before glucose loading (NIDD: 266 +/- 37, GI: 252 +/- 32, NG: 90 +/- 21 IU/l; Kruskal-Wallis H = 7.03; p = 0.03), but not after 2 hours (NIDD: 297 +/- 42, GI: 275 +/- 36, NG: 204 +/- 113 IU/l; ns).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Increase of angiotensin converting enzyme activity during oral load of glucose]. 133 58

The morphological changes of acute lung injury of rabbits, particularly the ACE content in the vascular endothelium of lung were studied with immunohistochemical methods and Q-970 image analysor. The activity of ACE in serum collected from the arteries was also estimated. The results showed that during the process of acute lung injury, the lung vascular endothelium was severely damaged with an obvious decrease of ACE content and activity. It indicates that decrease of ACE content and activity may play an important role in the pathogenesis of acute lung injury and may also be the sensitive criteria in expressing damage of the vascular endothelium in the lungs.
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PMID:[Immunohistochemical observation of angiotensin converting enzyme in acute lung injury]. 133 85

The pattern of inhibition of tissue angiotensin converting enzyme (ACE) was studied in rats after acute and chronic (14 days) oral administration of perindopril. Free and total tissue ACE were measured by quantitative in vitro autoradiography using [125I]-351A as a radioligand and compared with plasma ACE and pressor responses to angiotensin I. Following oral perindopril, plasma perindoprilic acid and the pattern of inhibition of plasma ACE activity were maximal at 1 to 2 h, but recovered over 24 h. However, inhibition of the pressor response to angiotensin I was more prolonged, being 95% at 4 h, but had not fully recovered by 24 h. Acutely, ACE was markedly inhibited in renal proximal tubules, lung parenchyma, and aortic wall. At 24 h, ACE in these tissues had only partially recovered. Angiotensin converting enzyme in vascular endothelium of other organs showed a similar pattern of inhibition. In contrast, ACE in testicular seminiferous tubules was unaffected by perindopril. After chronic (14 days) administration of perindopril, total plasma ACE increased 3-fold, of which 49% was occupied by the inhibitor. Total tissue ACE in kidney and aorta did not change, and the pattern of inhibition observed acutely was maintained during chronic treatment. These results demonstrate a prolonged effect of ACE inhibitors on tissue ACE that may better explain the time course of these drugs than the changes in plasma ACE or plasma levels of the drugs.
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PMID:Acute and chronic effects of perindopril on tissue angiotensin converting enzyme activity. 164 81

The pulmonary and hepatic clearances of the synthesized angiotensin converting enzyme (ACE) substrate, hippuryl-L-histidyl-L-leucine (HHL) were evaluated by applying the multiple sites of input method and the recirculation pharmacokinetic model. Rats received a constant rate infusion via the carotid artery, jugular vein or portal vein in the absence or presence of the ACE inhibitor, captopril. Blood samples were collected from the femoral artery. The organ extraction ratio was calculated from the steady-state plasma concentrations and the mean organ transit time was computed as the difference in the mean residence times for various administration routes. Pronounced elimination in the lung and liver was observed in the absence of captopril. Pulmonary metabolism was completely depressed in the presence of captopril while the hepatic elimination was little affected. This suggests that the pulmonary elimination was entirely ascribed to ACE while there exists an alternative elimination process in the liver. The mean cardiopulmonary transit time was very short, indicating the pulmonary elimination of HHL may take place on the surface of the vascular endothelium. The evaluation of the pulmonary elimination of HHL described in this paper indicates a simple in vivo method for assessing the pharmacological effect of ACE inhibitors. The present pharmacokinetic approach will be useful for the quantification of drug disposition in individual organs in vivo.
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PMID:Pulmonary and hepatic disposition of hippuryl-L-histidyl-L-leucine. 164 13

ACE, a carboxypeptidase that hydrolyses angiotensin-1 to angiotensin-2, is widely found in human tissues including vascular endothelium. It is also produced by epithelioid cells of sarcoid granulomata which elevate serum ACE, a useful test of active sarcoidosis, despite its less than optimal sensitivity and specificity. It is not known why ACE production is increased in only certain granulomatous disorders. The explanation may assist our understanding of the pathogenesis of sarcoidosis.
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PMID:A review of angiotensin converting enzyme in health and disease. 167 5

Proper classification of patients into diffuse cutaneous and limited cutaneous subsets and the anticipation of complications are the keys to the management of subjects with systemic sclerosis (scleroderma). Patients with early diffuse disease and rapidly progressive skin thickening are at highest risk of developing serious disease of the internal organs (intestine, lung, heart, kidney) and should be considered for disease modifying treatment. The targets of the disease and sites of possible intervention are vascular endothelium (vasoprotective agents), mononuclear cell subsets (immunosuppressive agents), and fibroblasts (colchicine, D-penicillamine). A number of new agents with sound scientific rationale are currently undergoing therapeutic trials. Much can be done to improve the lifestyle of those with scleroderma. The most dramatic recent development is the ability to reverse kidney disease by the prompt use of angiotensin converting enzyme inhibitors and modern methods of renal dialysis and transplantation. Scleroderma is not a hopeless disease.
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PMID:Treatment of systemic sclerosis. 175 Aug 1

The tissue protective effect of iloprost against anoxia was studied in the isolated perfused rat lung. The change in angiotensin converting enzyme activity was taken as a sign of the biochemical activity of pulmonary vascular endothelium and was measured by bioassay of the vasoconstrictor effects of angiotensin I and angiotensin II. A significant decrease in angiotensin converting enzyme activity was observed in the lungs incubated with Krebs alone and exposed to anoxia for 2 h. The decrease in angiotensin converting enzyme activity following anoxia for 2 and 24 h was prevented by prior pretreatment with iloprost. The pulmonary vasoconstrictor effect of angiotensin II was significantly enhanced following anoxia and iloprost prevented this potentiation. The prevention by iloprost of the decrease in angiotensin converting enzyme activity and increase in the pressor response to angiotensin II was attributed to damage of pulmonary vascular endothelium during anoxia. Possible underlying mechanisms are discussed.
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PMID:Iloprost (ZK 36374) prevents angiotensin I conversion in the isolated perfused rat lung against anoxia. 242 44

In order to gain insight into the local actions of angiotensin II (ANG II) we have determined the distribution of a component of the effector system for the peptide, the ANG II receptor, and that of an enzyme-catalysing ANG II formation, angiotensin converting enzyme (ACE), by in vitro autoradiography in several target tissues. The superagonist ANG II analog, 125I[Sar1]ANG II, or the antagonist analog, 125I[Sar1,Ile8]ANG II, were used as specific radioligands for ANG II receptors. A derivative of the specific ACE inhibitor, lysinopril, called 125I-351A, was used to label ACE in tissues. In the adrenal, a high density of ANG II receptors occurs in the glomerulosa zone of the cortex and in the medulla. ACE is also localized in these two zones, indicating that local production of ANG II may occur close to its sites of action in the zona glomerulosa and adrenal medulla. In the kidney, a high density of ANG II receptors is associated with glomeruli in the cortex and also with vasa recta bundles in the inner stripe of the outer medulla. ACE is found in very high concentration in deep proximal convoluted tubules of the cortex, while much lower concentrations of the enzyme occur in the vascular endothelium throughout the kidney. In the central nervous system three classes of relationships between ANG II receptors and ACE are observed: In the circumventricular organs, including the subfornical organ and organum vasculosum of the lamina terminalis, a high concentration of both components occurs. Since these structures have a deficient blood-brain barrier, local conversion of circulating angiotensin I (ANG I) to ANG II may contribute to the action of ANG II at these sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Local actions of angiotensin II: quantitative in vitro autoradiographic localization of angiotensin II receptor binding and angiotensin converting enzyme in target tissues. 243 88


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