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 clinical use of nonsteroidal anti-inflammatory drugs is gaining wide acceptance and acute oliguric renal failure in association with the administration of ibuprofen has been reported. This study was designed to evaluate the renal effects of intermittent versus continuous intravenous infusion of ibuprofen (Motrin) over a 24-h period in the anesthetized non-pregnant baboon. A total of 50 mg/kg of ibuprofen was either infused continuously or given as a bolus in four divided doses (intermittent). Control animals received only normal saline. Mean aortic pressure showed a tendency to decrease with time in all groups studied with a significant decrease occurring in the infusion group. There were no significant changes in the renal artery flow, renal resistance, central venous pressure and heart rate within the groups. Serum urea nitrogen decreased and was significantly different from the baseline value at 24 h in the infusion group. Serum creatinine, however, showed no such changes. Although, urinary output and creatinine clearance showed a tendency to decrease in the treated groups, it was not significantly different. Plasma renin activity decreased from 9.95 to 2.3 ng/ml/hr in the control group but showed no significant changes in others. Serum levels of angiotensin converting enzyme were well maintained. The circulating levels of ibuprofen reached a steady state after 2 h in the infusion group. The results of this study demonstrate that continuous infusion of ibuprofen does not possess an advantage over its intermittent administration. Despite the modifications we have observed in renal flow and function, this drug appears to be safe in the dose levels we have used in these experiments.
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PMID:Renal effects of intermittent versus continuous infusion of ibuprofen in the primate. 784 93

ACE inhibitors have been shown to worsen the kidney damage occurring distal to a renal artery stenosis. To determine if this effect was due to the decrease of arterial pressure or to an inhibition of the formation of angiotensin, we compared the effects of equihypotensive doses of an angiotensin converting enzyme inhibitor (enalapril) and a long-acting calcium antagonist (Ro 40-5967) in 2K-1C rats. The rats were treated for five weeks with either enalapril, Ro 40-5967, or were left untreated. A group of sham operated rats was used as control. At the end of the five-week treatment period, proteinuria, plasma urea and creatinine were measured and quantitative morphometry of the clipped and unclipped kidneys was performed. Ro 40-5967, despite an absence of inhibition of the renin-angiotensin system, worsened the lesions of the clipped kidney to the same extent as enalapril. In contrast, the effects of both drugs on the unclipped kidney were different. Ro 40-5967, and not enalapril, increased the weight and the glomerular surface area of the unclipped kidney. Ro 40-5967 did not change the glomerulosclerosis index, which was improved by enalapril. In contrast with enalapril, Ro 40-5967 decreased plasma urea and creatinine concentrations. Only enalapril decreased proteinuria which originated from the unclipped kidney as shown by nephrectomy experiments. We conclude that during ACE inhibition the fall in renal perfusion pressure seems to be the main determinant of the renal damage distal to a renal artery stenosis, independently of a blockade of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium blockade versus ACE inhibition in clipped and unclipped kidneys of 2K-1C rats. 796 54

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

Uric acid, or more correctly (at physiological pH values), its monoanion urate, is traditionally considered to be a metabolically inert end-product of purine metabolism in man, without any physiological value. However, this ubiquitous compound has proven to be a selective antioxidant, capable especially of reaction with hydroxyl radicals and hypochlorous acid, itself being converted to innocuous products (allantoin, allantoate, glyoxylate, urea, oxalate). There is now evidence for such processes not only in vitro and in isolated organs, but also in the human lung in vivo. Urate may also serve as an oxidisable cosubstrate for the enzyme cyclooxygenase. As shown for the coronary system, a major site of production of urate is the microvascular endothelium, and there is generally a net release of urate from the human myocardium in vivo. In isolated organ preparations, urate protects against reperfusion damage induced by activated granulocytes, cells known to produce a variety of radicals and oxidants. Intriguingly, urate prevents oxidative inactivation of endothelial enzymes (cyclooxygenase, angiotensin converting enzyme) and preserves the ability of the endothelium to mediate vascular dilatation in the face of oxidative stress, suggesting a particular relationship between the site of urate formation and the need for a biologically potent radical scavenger and antioxidant.
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PMID:Towards the physiological function of uric acid. 832 34

In a series of 174 patients with advanced chronic renal failure due to well defined primary nephropathies, we retrospectively studied factors influencing the rate of progression of renal failure. Using multivariate analysis of variance, we examined the role of gender, type of nephropathy, body mass index, age, protein intake quantified from 24-hour urine urea excretion, blood pressure and need for antihypertensive treatment (including a group of patients treated with ACE inhibitors) on the rate of decline of creatinine clearance (Ccr). We found a prominent and independent influence of sex and type of nephropathy, and to a lesser extent of mean arterial pressure and protein intake. Overall, these covariates were significantly correlated with the slope of decline in creatinine clearance (n = 174; r = 0.61; r2 = 0.37; p < 0.001) indicating that nearly 40% of the total variation in the slope could be predicted by these covariates. The influence of blood pressure was more readily apparent in males, and in patients with the opposite extreme values, i.e., chronic tubulointerstitial nephritis (CIN) and hypertensive angionephrosclerosis (ANS). The effect of protein intake was marginal and limited to patients with CIN and chronic glomerulonephritis (CGN). Effect of gender was important with a progression nearly two times faster in males than in females, and was mostly apparent in polycystic kidney disease (PKD) and in CGN. Type of nephropathy was also determinant. The rate of progression was steeper in Alport's syndrome than in CGN and ANS, and in the latter than in PKD and CIN (slope: CIN = PKD < CGN = ANS < Alport).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factors affecting progression in advanced chronic renal failure. 833 58

Although bronchoalveolar lavage (BAL) is useful in studying a variety of lung diseases, it results in substantial dilution of cells and soluble proteins recovered from the lower respiratory tract. Surprisingly little is known about regional differences in BAL recovery in normals and patients with lung disorders. In order to assess regional differences in BAL in normals, we performed a prospective study of BAL in twenty non-smoking volunteers. With the subjects supine, BAL was performed in the right middle lobe (RML), right lower lobe (RLL) and Lingula (LING). The volumes recovered, cell numbers, and angiotensin converting enzyme (ACE) activities were determined separately for each BAL site. ACE was chosen as a representative soluble protein found in the lower respiratory tract which was easily measured in the BAL of normals. BAL volumes recovered from the RLL were significantly smaller than from the RML or LING, perhaps related to the dependent location of the RLL (P = 0.0002). The concentration of ACE and cells recovered per ml of BAL were significantly greater in the RLL than either the RML or LING (P = 0.05). In contrast, the total numbers of cells and total ACE recovered were similar from all sites sampled. This suggests that the differences in measured concentrations were due to different fluid recovery from these sites, resulting in variable dilution of proteins and cells. Urea measurement has been proposed as a means to quantify the epithelial lining fluid (ELF) volume sampled by BAL and estimate the actual concentrations of proteins present in the lower respiratory tract (J Appl Physiol 1986; 60:532-538).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interlobar variation in the recovery of bronchoalveolar lavage fluid, cell populations, and angiotensin-converting enzyme in normal volunteers. 838 93

The study describes the changes in basic hemodynamic parameters after long-term antihypertensive therapy with cilazapril--a new ACE inhibitor lacking a sulfhydryl group--in hypertensive patients and the drug effects on renal function, glucose tolerance and lipid metabolism. 30 patients (18 males, 12 females, mean age: 53.3 +/- 18 years) with mild to moderate essential hypertension were studied. The following determinations were performed in patients, before and after 4.5 months of cilazapril monotherapy at a dose of 5 mg/24 h: (a) antihypertensive action of the drug (arterial pressure at rest and during a 24-hour recording); drug effects on left ventricular (LV) mass index; its contractility indexes (%FS, EF) and the left atrial emptying index were studied by means of echocardiography; (b) plasma insulin concentration during oral glucose tolerance tests, in the fasting state, after the administration of 75 g glucose per os, as well as the changes in the insulinogenic index and the 6-keto-PGF1 alpha/TXB2 ratio, and (c) drug effect on renal function (urea, creatinine, uric acid, plasma electrolytes), blood lipid profile (total cholesterol, triglycerides, HDL-CH) and serum transaminases. Long-term drug administration exhibits an effective antihypertensive action, without causing reflex tachycardia and also reduces the LV mass index without affecting its EF, while improving its diastolic function. It does not significantly affect the various biochemical parameters, and achieves glucose regulation, both in the fasting state and after glucose loading, with a decrease in the insulinogenic index, and simultaneously increases the 6-keto-PGF1 alpha/TXB2 ratio. The existence of a direct cause-effect relationship between the changes in the above hormone systems is possible.
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PMID:Hemodynamic and biochemical changes after chronic administration of cilazapril to hypertensive patients. 840 51

The role of angiotensin converting enzyme (ACE) inhibitors in improving insulin-mediated glucose uptake has been described. However, their effects on long-term glucose control in diabetes mellitus are less well established. This study examines the effect of 4 months of captopril treatment on blood pressure (BP) and glucose control in 130 subjects with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. Therapy for glycemic control was adjusted during a 3 month period prior to entry into active BP treatment and was not changed during 4 months of captopril administration. Fasting blood glucose and sitting BP were measured before and at 1, 2, 3, and 4 months of captopril monotherapy. Hemoglobin (Hb) A1c, serum electrolytes, creatinine, total cholesterol, and triglycerides were measured before and at 4 months. There were significant reductions in fasting blood glucose from baseline at 1 month (P < .01) and further stepwise decreases in values at 2, 3, and 4 months. Differences in glucose from month to month were highly significant. HbA1c was stable over a 3-month pretrial period, then decreased (P < .001) from baseline at 4 months of active treatment. Mean serum potassium increased from 4.4 to 4.7 (P < .001) at month 4 and there was an inverse correlation (r = -0.2, P < .025) between changes in potassium and HbA1c. Total serum cholesterol fell (P < .01) at month 4 of treatment. Serum creatinine and blood urea were unchanged, but of 18 patients with mild proteinuria pretrial, 12 of 18 were negative for protein at 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of the angiotensin converting enzyme inhibitor captopril on metabolic control in non-insulin-dependent diabetes mellitus. 851 57

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


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