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)

Tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) is driven by increased levels of angiotensin II (Ang II). In this study, we examined the time course of the fibrotic process in rats with UUO and explored the effect of delayed administration of an angiotensin converting enzyme (ACE) inhibitor, enalapril, on the tubulo-interstitial fibrosis of obstructive uropathy. Rats were sacrificed at 3, 5, 8, or 10 days after UUO was initiated. Some rats did not receive treatment, whereas others were treated with enalapril from day 4 to day 8 or from day 6 to day 10 after the onset of UUO. The levels of mRNA for transforming growth factor beta 1 (TGF-beta 1), collagen type IV (collagen IV), and tissue inhibitor of metalloproteinase (TIMP-1) were measured at each time point by reverse transcription-polymerase chain reaction (RT-PCR). The relative volume of the tubulointerstitium (Vv) was measured by a point-counting method. Monocyte/macrophage infiltration and collagen IV protein deposition were examined histologically using specific antibodies. There were significant increases in TGF-beta 1, TIMP-1, and collagen IV mRNAs in the obstructed kidney. Treatment with enalapril on day 4 through day 8 or on day 6 through day 10 significantly reduced the elevated mRNA levels of these compounds in the obstructed kidney. Histological studies showed augmented Vv, monocyte/macrophage infiltration, interstitial alpha-smooth muscle actin expression, and collagen IV protein deposition on days 3, 5, 8, or 10 of UUO; enalapril treatment from day 4 to 8 or from day 6 to 10 halted and to an extent reversed these increases. These data suggest that enalapril administration after several days of UUO is an effective means of preventing the progression of tubulointerstitial fibrosis of obstructive uropathy.
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PMID:Delayed treatment with enalapril halts tubulointerstitial fibrosis in rats with obstructive nephropathy. 869 32

Obstructive uropathy impairs nephron growth and function and is a major cause of end-stage renal disease in both adults and children. The major focus of this review article is to examine the evidence implicating a role for the kallikrein-kinin system in the pathophysiology of obstructive uropathy. Recent in vivo studies using specific kinin receptor antagonists and transgenic animals overexpressing or lacking various components of the kallikrein-kinin system have documented that kinins are involved in the regulation of renal function and blood pressure. Multiple roles have been proposed for kinins in obstructive uropathy. Renal kallikrein gene expression is suppressed in the kidney with chronic (>7 days) complete ureteral obstruction. In contrast, ureteral obstruction stimulates renin expression, creating a state of intrarenal angiotensin excess and kinin deficiency, which plays an important role in mediating the increased renal vascular resistance and decreased renal blood flow in the obstructed kidney. In addition to their hemodynamic effects, kallikrein and kinins influence tubular functions. For example, kallikrein influences urinary acidification in the distal nephron, suggesting that dysregulation of kallikrein expression may contribute to the acidification defect in the obstructed kidney. Also, kinins exert direct diuretic and natriuretic effects in the collecting duct and may be important in mediating the post-obstructive diuresis after the relief of urinary obstruction. The kinin substrate, kininogen, is a potent inhibitor of lysosomal cysteine proteases. Unlike kallikrein, kininogen synthesis is upregulated in the kidneys and liver of animals with urinary obstruction. By neutralizing cysteine proteases, kininogen may protect the tubular epithelium of obstructed nephrons from excessive apoptosis. The beneficial actions of kinins and kininogens on renal hemodynamics, tubular function, and cell survival suggest that strategies aimed at increasing intrarenal kinins, eg, ACE-kininase II inhibitors and kallikrein gene therapy, may represent a useful adjunct in the medical treatment of obstructive uropathy.
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PMID:The kininogen gene family in obstructive uropathy. 981 54

Chronic renal failure (CRF) is the irreversible deterioration of renal function that gradually progresses to end stage renal disease (ESRD). The chief causes of CRF include obstructive uropathy, primary glomerular diseases, reflux nephropathy and hypoplastic or dysplastic kidneys. Progressive hyperperfusion and hyperfiltration causes increasing glomerular injury and further renal damage. Symptoms of CRF are usually seen when GFR is between 10-25% of normal. Children with severe CRF often suffer from failure to thrive, growth retardation, acidosis, anemia and renal osteodystrophy. Management of CRF aims at retarding progression of renal damage and treatment of complications related to renal dysfunction. Measures suggested to retard progression include protein restriction, strict control of hypertension, use of angiotensin converting enzyme inhibitors and control of hyperlipidemia. Appropriate amounts of protein and calories are recommended to prevent growth failure. Nutritional supplements are often required. The availability of recombinant erythropoietin, calcitriol and human growth hormone has significantly improved the management of these patients. Once ESRD supervenes, renal replacement therapy in the form of chronic peritoneal or hemodialysis and transplantation is necessary.
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PMID:Evaluation and treatment of chronic renal failure. 1079 66

Obstructive nephropathy is a relatively common entity that is treatable and often reversible. It occurs at all ages from infancy to elderly subjects. Obstructive uropathy is classified according to the degree, duration and site of the obstruction. It is the result of functional or anatomic lesions located in the urinary tract. The causes of obstructive uropathy are many. Obstruction of the urinary tract may decrease renal blood flow and the glomerular filtration rate. Several abnormalities in tubular function may occur in obstructive nephropathy. These include decreased reabsorption of solutes and water, inability to concentrate the urine and impaired excretion of hydrogen and potassium. Renal interstitial fibrosis is a common finding in patients with long-term obstructive uropathy. Several factors: macrophages, growth factors, hypoxia, cytokines are involved in the pathogenesis of interstitial fibrosis. It has been shown that ACE inhibitors ameliorate the interstitial fibrosis in animals with obstructive uropathy.
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PMID:Obstructive nephropathy. 1083 Jan 73

To investigate the role of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on prevalence and progression of disease in children with chronic renal failure (CRF), we determined the ACE I/D genotype in 95 children with CRF due to renal malformations (hypo-/dysplasia, obstructive uropathy, reflux nephropathy; n = 59), other congenital or hereditary diseases (n = 23), or acquired glomerular disorders (n = 13), who had been followed prospectively over a 2-year period. CRF progression rate was followed in each individual by linear regression analysis of estimates of glomerular filtration rate (GFR) obtained every 2 months. Actuarial renal 'survival' analysis was performed, using a GFR loss of 10 ml/min per 1.73 m2 as a cutoff point. The distribution of the ACE genotype did not differ among the disease groups. There was also no difference in ACE genotype distribution between the patients and a control group of healthy Caucasian children (n = 163). Among the children with renal malformations, the 2-year renal survival was significantly lower in those with the DD genotype (61%) than in patients with ID or II genotype (89%, P < 0.01). In the other disease groups, the ACE I/D genotype was not predictive of CRF progression. In a multivariate analysis of risk factors, the adverse effect of the DD genotype (risk ratio 10.2, P < 0.05) was independent of and additive to those of arterial hypertension (RR 13.2, P < 0.001) and gross proteinuria (RR 4.7, P < 0.05). We conclude that the ACE DD genotype is a significant risk factor for children with congenital renal malformations to develop progressive CRF. The effect of the ACE polymorphism in this patient group is independent of hypertension and proteinuria.
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PMID:Impact of ACE I/D gene polymorphism on congenital renal malformations. 1135 81

Complete ureteral obstruction in rats rapidly leads to renal interstitial expansion and fibrosis and this process is ameliorated by concomitant angiotensin converting enzyme inhibition (ACEI). However, models of intervention initiated after unilateral ureteral obstruction (UUO) release may be more analogous to human obstructive renal disease where treatment could more reasonably follow the discovery of obstructive uropathy as compared to models where treatment is initiated at the time of experimentally induced obstruction. We studied interstitial changes in rats before and after release of UUO and examined the effect of ACEI with 200mg/L of enalapril (E) in the drinking water on these changes. Rats were sacrificed after 10 (n=10) and 20 (n=10) days (D) of UUO or 10D after release of 10D of UUO (n=18). Eleven rats received E for 10D after UUO release. Cortical interstitial volume fraction [Vv(I/C)] measured by point counting was increased at 10D (0.32 +/- 0.05) and 20D (0.41 +/- 0.05) of UUO compared to contralateral and sham-operated kidneys (both 0.05 +/- 0.01, ANOVA, p <0.001). Vv(I/C) 10D after release from 10D of UUO (0.26 +/- 0.04) was lower than that of 10D of UUO (p<0.05) and much lower than those with 20D of UUO (p<0.001). However, rats treated with E from the time of UUO release had lower Vv(I/C) (0.21 +/- 0.07) than UUO released E untreated rats (p<0.05). Release of UUO initiates regression of interstitial expansion in rats. ACEI with enalapril significantly accelerates reversal of interstitial expansion after UUO release. This could have important implications for treatment of obstructive nephropathy in humans.
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PMID:Enalapril accelerates remodeling of the renal interstitium after release of unilateral ureteral obstruction in rats. 1277 69

To understand pitfalls and limitations in adult renography, it is necessary to understand firstly the physiology of the kidney, especially the magnitude and control of renal blood flow, glomerular filtration rate and tubular fluid flow rate, and secondly the pharmacokinetics and renal handling of the three most often used tracers, Tc-99m-mercaptoacetyltriglycine (MAG3), Tc-99m-diethylene triamine pentaacetic acid (DTPA) and Tc-99m-dimercaptosuccinic acid (DMSA). The kidneys may be imaged dynamically with Tc-99m-MAG3 or Tc-99m-DTPA, with or without diuretic challenge, or by static imaging with Tc-99m-DMSA. Protocols are different according to whether the kidney is native or transplanted. Quantitative analysis of dynamic data includes measurement of renal vascularity (important for the transplanted kidney), absolute tracer clearance rates, differential renal function (DRF) and response to diuretic challenge. Static image reveals functional renal parenchymal damage, both focal and global, is useful in the clinical management of obstructive uropathy, renal stone disease and hypertension (under angiotensin converting enzyme inhibition), and is the preferred technique for determining DRF. Diagnosis based on morphological appearances is important in transplant management. Even though nuclear medicine is now in the era of hybrid imaging, renal imaging remains an important subspecialty in nuclear medicine and requires a sound basing in applied physiology, the classical supporting discipline of nuclear medicine.
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PMID:Pitfalls and Limitations of Radionuclide Renal Imaging in Adults. 2627 54