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 primary results of a three-year prospective, double-blind, placebo-controlled trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti-hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors (J Am Soc Nephrol 3:335, 1992). The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis. Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m2]. Twenty-four hour urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and isotopically determined GFR were measured at baseline and six month intervals. Glycemic control and blood pressure regulation were assessed every three months. The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline (UAE > 300 mg/24 hr) as compared to patients with baseline sub-clinical proteinuria (UAE < or = 300 mg/24 hr). Antihypertensive treatment with enalapril preserved GFR significantly better (P < 0.01) in the patients with sub-clinical proteinuria at baseline (UAE < or = 300 mg/24 hr) than other antihypertensive treatments which excluded the ACE inhibitor. Furthermore, only 7% of the enalapril-treated group progressed to clinical albuminuria compared to 21% of control treated patients. Although the enalapril-treated group had a lower mean blood pressure during the maintenance period, no correlation between blood pressure (systolic, diastolic or mean arterial) and rate of change of GFR was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal protective effects of enalapril in hypertensive NIDDM: role of baseline albuminuria. 815 85

In order to evaluate the mid-term effects of amlodipine, a 1,4-dihydropyridine calcium antagonist, as well as its effects on the renin-angiotensin-aldosterone system (RAAS), on water and electrolyte balance, on urinary excretion of albumin (UAE) and on lipid metabolism, thirteen hypertensive patients (2 M, 11 F, mean age 54 years) were studied in the course of 24 weeks of therapy with amlodipine at 5-10 mg/day. Pre-therapy and periodically during therapy, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded in the sitting orthostatic positions (2 measurements). Laboratory tests were performed at times O and at 24 wks with the patients fasting for at least 12 h in the recumbent position. The tests included: plasma renin activity (PRA), plasma aldosterone (PA), serum angiotensin converting enzyme (SACE), blood urea nitrogen (BUN), blood creatinine, plasma electrolytes (Na, K, Cl), triglycerides, total cholesterol (TC) and HDL-cholesterol (HDLC), along with 24-h urine samples (with sterile urine) to determine UAE. The results of this study demonstrate that SBP, DBP and HR were significantly reduced during the 24 wks of therapy. The water and electrolyte and renal function were not modified. After treatment the levels of TC were significantly reduced. No change was observed in the RAAS, while the mean levels of UAE were reduced though not significantly. In conclusion, amlodipine was shown to be effective for the therapy of hypertension; it does not cause reflex tachycardia even in mid-term therapy and was effective in reducing TC levels.
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PMID:Amlodipine in ambulatory hypertensive patients: humoral and haemodynamic effects. 822 98

A series of monoamidic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic and 1,2-cyclopentanedicarboxylic acids bearing either a carboxylic, sulfhydrylic, or hydroxamic group in the side chain were synthesized and evaluated in vitro for their inhibitory activity against angiotensin converting enzyme. The compounds were designed as potential ACE inhibitors of novel structure, assuming that a monoamidic residue of an 1,2-cyclomethylenedicarboxylic acid could be an alternative structure to the acylproline moiety, the carboxyl-terminal portion common to various ACE inhibitors. The most active compounds were found in the hydroxamic derivatives of cyclohexane series; within this series of derivatives a marked increase of potency was caused by alkylation of the amidic nitrogen with a methyl or ethyl group. Therefore enantiomers of the selected hydroxamic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic acid were prepared by two different chiral synthetic routes and evaluated in vitro for their ACE inhibitor potencies. The active enantiomers both of the cis series (21a, 21c) and trans series (16b, 16d) were found to have all R configuration at the C-2 and R or S configuration at the C-1, while in the classical ACE inhibitors S configuration at the terminal carboxylate (corresponding to the C-1 of our compounds) is strictly required for activity. The most potent compound of the series was (1S,2R)-cis-2[[[2-(hydroxyamino)-2-oxoethyl]methylamino]carbonyl] cyclohexanecarboxylic acid (21a) with an IC50 value of 7.0 nM compared with the value of 3.0 nM for captopril. Further 21a was shown to be highly selective and competitive ACE inhibitor. These results indicate that this non-amino acid structure of inhibitors meets the ACE active site requirements for the binding. The binding compatibility of the most active compounds with a model of ACE active site was evaluated by molecular modeling techniques.
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PMID:1,2-Cyclomethylenecarboxylic monoamide hydroxamic derivatives. A novel class of non-amino acid angiotensin converting enzyme inhibitors. 845 98

A 39-year-old woman was consulted to our hospital because of renal failure on October 1992. A chest X-ray showed no abnormal shadow. Subsequently, she was under conservative treatment until December 1993, when she began to notice clouded vision. The iridocyclitis in both eyes was diagnosed by a ophthalmologist. She was admitted to our hospital for the purpose of a renal biopsy. Laboratory tests revealed renal failure: a creatinine clearance of 24.5 ml/min, a serum level of creatinine of 3.2 mg/ml and blood urea nitrogen of 38.7 mg/dl. The angiotensin converting enzyme was 17.6 IU/ml (normal 8.3 approximately 21.4 IU/ml), but lysozyme was 49.5 micrograms/ml (normal 5.0 approximately 10.2). Mantoux's reaction was negative. 57Ga scintigram showed abnormal uptakes on eyes, bilateral salivary gland, both thighs, both kidneys, and in a part of lung field. A percutaneous renal biopsy revealed non-caseating histiocytic granulomas with diffuse infiltration of lymphocytes and neutrophils into interstitium. Glomeruli were ischemic and mild endocapillary proliferations with pericapsular fibrosis were seen. Both of transbronchial lung biopsy (TBLB) and skin biopsy also revealed non-caseating histiocytic granulomas. Oral administration of prednisolone, 40 mg/day, improved the level of serum creatinine and lysozyme. Sarcoidosis is a granulomatous disease of unknown etiology that may involve any organ or tissue of the body. The clinical picture dominating in adults is the one with pulmonary and mediastinal lymph node involvement, eye and skin lesions. Although the renal involvement were rarely encountered, the present case showed that the renal failure was one of the most important clinical feature in patient with sarcoidosis.
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PMID:[A case of sarcoidosis with renal failure as the main manifestation in granulomatous interstitial nephritis]. 856 2

1. In patients with congestive cardiac failure, treatment with angiotensin converting enzyme (ACE) inhibitors results in peripheral vasodilatation and an increase in cardiac output without an increase in heart rate, which suggests a positive inotropic effect. This cannot be explained by changes in angiotensin II and bradykinin concentrations that occur. ACE has been suggested to also metabolise vasoactive intestinal peptide (VIP), which is a positive inotrope. As VIP is synthesized by the heart and acts locally to increase cardiac output, we postulated that ACE inhibition would increase the myocardial concentration of VIP. 2. Male Sprague-Dawley rats received enalapril (2 mg/kg per day) in their drinking water or no therapy for 7 days. On day 7 the rats were anaesthetized and blood was sampled. Hearts and kidneys were then harvested and snap frozen by immersion in liquid nitrogen. Concentrations of VIP in plasma and tissue extracts were measured by radioimmunoassay. 3. Plasma and renal concentrations of VIP did not change in enalapril-treated rats. However, the myocardial concentration of VIP increased significantly in rats receiving enalapril compared with control animals (P < 0.0005). 4. We conclude that treatment with ACE inhibitors results in increased myocardial VIP concentrations and suggest that this may contribute to the improvement in cardiac function that occurs with these agents.
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PMID:Increases in the myocardial concentration of vasoactive intestinal peptide may explain the positive inotropic effect of angiotensin converting enzyme inhibitors. 880 Jun 3

The adult protein turn-over daily affects 250 grammes, which is equivalent to four times the average daily protein intake. Regulation of synthesis and catabolism appears to occur by independent ways. These systems are altered during the nephrotic syndrome and ultimately lead to a loss of total body nitrogen and a risk for malnutrition. Indeed, during the nephrotic syndrome, muscle protein synthesis is further impaired as the urinary protein losses increase. This may suggest that anabolic compounds are lost in the urine of such patients. A moderate protein restriction (0.8 g/kg BW/day) allows a reduction in proteinuria, as well as pharmacological agents (ACE inhibitors) and should therefore slow the progressive renal insult.
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PMID:[Nephrotic syndrome and protein metabolism]. 892 6

In patients with congestive cardiac failure, treatment with ACE inhibitors results in peripheral vasodilatation and an increase in cardiac output without an increase in heart rate, which suggests a positive inotropic effect. This cannot be explained by the changes in angiotensin II and bradykinin concentrations that occur. It has been suggested that ACE also metabolizes VIP, which is a positive inotrope. As VIP is synthetized by the heart and acts locally to increase cardiac output, we postulated that ACE inhibition would increase the myocardial concentration of VIP. Male Sprague-Dawley rats received enalapril (2 mg/kg/day) in the drinking water or no therapy for seven days. On day seven they were anaesthetized and blood sampled. The hearts and kidneys were then harvested and snap frozen by immersion in liquid nitrogen. Concentrations of VIP in plasma and tissue extracts were measured by radioimmunoassay. Plasma and renal concentrations of VIP did not change in the enalapril-treated rats. However, the myocardial concentration of VIP increased significantly in the rats receiving enalapril compared with control animals (p < 0.0005). We conclude that treatment with ACE inhibitors results in increased myocardial VIP concentrations and suggest that this may contribute to the improvement in cardiac function that occurs with these agents.
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PMID:Angiotensin-converting enzyme inhibition with enalapril increases the cardiac concentration of vasoactive intestinal peptide. 899 66

Benazepril (BP), an angiotensin convertive enzyme inhibitor, was administered orally once daily for 4 weeks to 31 dogs with mild to moderate (NYHA functional classes II and III) congestive heart failure caused from mitral insufficiency (MI). There were no significant changes in clinical signs, electrocardiogram findings, radiographical observations and plasma biochemical results in 11 dogs treated with placebo for 4 weeks. In 31 dogs treated with BP, appetite increased, and mean scores of heart failure signs, such as activity, exercise tolerance, cough and respiratory effort, were significantly improved. No dog displays signs suggesting systemic hypotension. One dog died suddenly on the 26th day of treatment with BP. This dog had good vigor and appetite till the evening before the death, and cough and exercise tolerance had been gradually improving. The heart rate and ECG parameters of BP treated dogs did not change significantly, but length of long axis of the heart decreased. In plasma biochemical tests, plasma urea nitrogen (UN) levels did not change significantly, and plasma creatinine (CRE) levels increased slightly within the normal ranges during BP trial. Two dogs had higher plasma UN levels with slightly higher plasma CRE levels, but had normal general condition and other biochemical results. Plasma ACE activity decreased to 57.3% of pre-treatment level at 4 weeks after BP treatment. It is concluded that BP monotherapy was efficacious at least in dogs with relatively low grade congestive heart failure caused by MI.
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PMID:Efficacy of monotherapy with benazepril, an angiotensin converting enzyme inhibitor, in dogs with naturally acquired chronic mitral insufficiency. 927 44

The present study was designed to investigate the effect of captopril, a sulfhydryl (-SH) containing ACE inhibitor and lisinopril, a non-SH containing ACE inhibitor, on ischaemia-reperfusion-induced renal injury in rats and to study the involvement of the free radical scavenging property of captopril in its renoprotective effect. Bilateral renal artery occlusion was induced for 30 min followed by reperfusion for 24 h. Blood samples were taken from retro orbital sinus before surgery and at 24 h after reperfusion for blood urea and blood creatinine estimation. After completion of 24 h of renal reperfusion the carotid artery was cannulated and the mean arterial blood pressure (MABP) was recorded. The left kidney was used for histological examination. The right kidney was utilised for estimation of mitochondrial thiobarbituric acid reactive substances (TBARS). Renal ischaemia, followed by reperfusion, significantly increased blood urea nitrogen (BUN) and blood creatinine. However, creatinine clearance decreased markedly. Captopril administered before renal artery occlusion or immediately after reperfusion and lisinopril pre-treatment significantly attenuated the increase in BUN and blood creatinine. Creatinine clearance was markedly better in captopril-treated animals as compared to lisinopril-treated rats. Captopril significantly decreased the degree of tubular necrosis, haemorrhagic streaks and urinary casts. Lisinopril treatment decreased tubular necrosis and urinary casts but no marked effect on haemorrhagic streaks was noted. Administration of captopril before ischaemia or just after reperfusion significantly reduced the elevated concentration of mitochondrial TBARS but no such decrease was noted in lisinopril-treated rats. Based on these results it may be concluded that captopril and lisinopril markedly protected against ischaemia-reperfusion-induced renal injury and any additional renoprotective effect of captopril may be ascribed to its free radical scavenging properties.
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PMID:Effect of angiotensin converting enzyme inhibitors on ischaemia-reperfusion-induced renal injury in rats. 950 76

The nephrotic mouse (ICGN strain) is a useful model for progressive nephrotic syndrome (NS). In the present study, we demonstrated the preventive effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, on the progression of renal dysfunction and tubulo-interstitial fibrosis in the NS mice. Administration of enalapril (5 mg/dL in drinking water) to the 4-week-old NS mice for a 4-week-period did not improve their nephrotic symptoms such as albuminuria and hypoalbuminemia, but significantly suppressed the increases in blood urea nitrogen and serum creatinine levels. Renal histopathology demonstrated that the administration of the ACE inhibitor significantly attenuated the progression of the tubular and interstitial lesions (tubular dilatation, luminal cast accumulation and interstitial expansion) rather than the glomerular sclerotic changes. The suppression of the increase in blood urea nitrogen level by enalapril depended on the attenuated tubular injury rather than on the unchanged glomerular matrix deposition. Immunohistochemical examination revealed that the administration of the ACE inhibitor suppressed the formation of myofibroblasts, identified by the alpha-smooth muscle actin-positive cells, in the interstitial spaces. Consequently, interstitial matrix deposition was significantly reduced in the NS mice treated with enalapril. From the results obtained with the spontaneous nephrotic model, we emphasize a possibility that ACE inhibitor may be effective for attenuating progression of renal dysfunction and fibrosis in human NS, even if the ACE inhibitor fails to improve nephrotic symptoms such as albuminuria and hypoalbuminemia.
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PMID:Preventive effect of ACE inhibitor on interstitial myofibroblast formation and matrix deposition in a nephrotic model. 960 36


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