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 mutant mouse strain Mpv17-/-, carries a retroviral germline integration that inactivates the Mpv17 gene. Mpv17-deficient mice develop progressive glomerulosclerosis and sensineural deafness at early age. Characteristic basement membrane alterations are found in both sites of pathology. Mpv17 is a peroxisomal protein involved in the metabolism of reactive oxygen species, yet its molecular function is unknown. Dysregulation of antioxidant enzymes and basal membrane components has been established in this model and successful therapeutic intervention with antioxidants prove the causal role of reactive oxygen species in the development of the disease phenotype. We here investigated if the Mpv17-/- mice might be hypertensive. Indeed, our study revealed that Mpv17-/- mice developed significant systemic hypertension and tachycardia between 4 weeks and 5 months of age, accompanied by polyuria and elevated natriuresis. Judging from serum and urine parameters, the hypertensive condition develops concomitantly with the renal disease. Biochemical and pharmacological studies that used the endothelin receptor antagonist bosentan and the angiotensin converting enzyme inhibitor cilazapril indicated no involvement of the endothelin and renin-angiotensin systems in this hypertension, suggesting a potential novel mechanism of blood pressure regulation in this new murine hypertension model. Thus, Mpv17-/- mice unravel an intriguing new association between a defect in reactive oxygen metabolism and the age-dependent development of hypertension.
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PMID:Age-dependent hypertension in Mpv17-deficient mice, a transgenic model of glomerulosclerosis and inner ear disease. 1067 53

Wistar fatty (WF) rats have a genetic predisposition to hyperglycemia, polyuria, hyperinsulinemia, hyperlipidemia, obesity and nephropathy. These phenotypic characteristics are similar to those observed in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. In this study, the effects of two types of renin-angiotensin system inhibitors, an angiotensin II type 1-receptor antagonist (AT1A) and an angiotensin I-converting enzyme inhibitor (ACEI), on renal injury in WF rats were studied during the progressive phase of diabetic nephropathy. An AT1A, candesartan cilexetil (1 mg/kg), and an ACEI, enalapril (10 mg/kg), were administered orally once a day for 12 weeks, beginning when the rats were 27-week-old and already showed diabetic nephropathy and obesity. Both drugs prevented an increase in proteinuria during the experimental period. Furthermore, after 4-week intervention, the levels of proteinuria were markedly lower in drug-treated rats. At the end of the experiment, both drugs prevented the development of glomerular lesions without affecting glucose metabolism and obesity. In conclusion, the inhibition of angiotensin II activity ameliorated both existing proteinuria and the progression of proteinuria, resulting in preservation of glomerular structure. Thus angiotensin II plays important roles in the development and the progression of nephropathy in genetically obese diabetic WF rats.
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PMID:Involvement of angiotensin II in progression of renal injury in rats with genetic non-insulin-dependent diabetes mellitus (Wistar fatty rats). 1138 46

Intracranial aneurysms (ICA) are a well-known feature of autosomal dominant polycystic kidney disease. There is only one report about ICA in an adult patient with autosomal recessive polycystic kidney disease (ARPKD). We observed a 2-year, 6-month old girl with ARPKD and multiple ICA. The family history is negative for kidney disease. The diagnosis of ARPKD was based on the typical findings in ultrasonography and computed tomography. Cystic ectasia of biliary ducts 6.3/4.8 cm in diameter was found in the liver. Arterial hypertension in a range of 140/100-170/120 mm Hg was registered. The child has polyuria, polydipsia and enuresis. Blood urea was 15 mmol/l, creatinine in a range of 120 to 75 micromol/l. One episode of vomiting, dizziness and lethargy was the reason for a brain magnetic resonance imaging. Multiple fusiform and saccular aneurysms in the branches of middle and posterior cerebral arteries were seen bilaterally. The girl is growing well without neurological symptoms during an observation period of 1.5 years. Blood pressure is well controlled with an ACE inhibitor (Enalapril 2.5 mg daily). It was concluded that ICA can be found in patients with ARPKD. Blood pressure control is essential to reduce the risk of intracranial hemorrhage.
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PMID:Intracranial aneurysms in a child with autosomal recessive polycystic kidney disease. 1179 94

Recently, we have demonstrated a direct correlation among hyperglycaemia, vascular dysfunction and eNOS post-translational regulation in non non-obese diabetic mice (NOD). Here, we evaluate the impact of two ACE-inhibitors therapy, zofenopril and enalapril in NOD mice. Insulin-dependent diabetes mellitus (IDDM) development was monitored weekly through glycosuria measurement. Zofenopril and enalapril were dosed at 0.5 mg/kg/die orally. Animals were sacrificed at different points and aortas used for western blotting or for tissue bath experiments. Bovine aortic endothelial cells in high glucose medium are treated with zofenoprilat or enalaprilat. Cells and supernatant were utilised for western blot analysis and for nitrite/nitrate determination, respectively. In ex-vivo experiments chronic administration of both drugs restored PE-induced contraction but not Isop-induced vasodilatation, however only zofenopril reduced caveolin-1 expression. In vitro, both drugs inhibited caveolin-1 expression and increased NOx production. However, zofenopril caused inhibition of both parameters at a concentration 200 fold lower than enalalpril. In vivo, zofenopril delays the onset of diabetic conditions of about 50%, and ameliorates polyuria. In conclusion our data suggest that ACE-inhibitor therapy may be useful in IDDM, in particular sulphydrylated inhibitor would display a better efficacy especially if administered early on the development of diabetes.
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PMID:ACE-inhibition ameliorates vascular reactivity and delays diabetes outcome in NOD mice. 1860 47

Alterations within the RAS (renin-angiotensin system) are pivotal for the development of renal disease. ACE2 (angiotensin-converting enzyme 2) is expressed in the kidney and converts the vasoconstrictor AngII (angiotensin II) into Ang-(1-7), a peptide with vasodilatory and anti-fibrotic actions. Although the expression of ACE2 in the diabetic kidney has been well studied, little is known about its expression in non-diabetic renal disease. In the present study, we assessed ACE2 in rats with acute kidney injury induced by STNx (subtotal nephrectomy). STNx and Control rats received vehicle or ramipril (1 mg. kg (-1) of body weight . day (-1), and renal ACE, ACE2 and mas receptor gene and protein expression were measured 10 days later. STNx rats were characterized by polyuria, proteinuria, hypertension and elevated plasma ACE2 activity (all P<0.01) and plasma Ang-(1-7) (P<0.05) compared with Control rats. There was increased cortical ACE binding and medullary mas receptor expression (P<0.05), but reduced cortical and medullary ACE2 activity in the remnant kidney (P<0.05 and P<0.001 respectively) compared with Control rats. In STNx rats, ramipril reduced blood pressure (P<0.01), polyuria (P<0.05)and plasma ACE2 (P<0.01), increased plasma Ang-(1-7) (P<0.001), and inhibited renal ACE(P<0.001). Ramipril increased both cortical and medullary ACE2 activity (P<0.01), but reduced medullary mas receptor expression (P<0.05). In conclusion, our results show that ACE2 activity is reduced in kidney injury and that ACE inhibition produced beneficial effects in association with increased renal ACE2 activity. As ACE2 both degrades AngII and generates the vasodilator Ang-(1-7), a decrease in renal ACE2 activity, as observed in the present study, has the potential to contribute to the progression of kidney disease.
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PMID:Reduction in renal ACE2 expression in subtotal nephrectomy in rats is ameliorated with ACE inhibition. 1969 82

This review explores the current model of sickle cell nephropathy and the limitations of the model. Renal abnormalities are common complications of sickle cell disease (SCD). Beginning in childhood, patients with SCD develop a urinary concentrating defect resulting in polyuria and a predisposition to nocturnal enuresis and dehydration. The current model of sickle cell nephropathy suggests that destruction of the renal medulla induces production of renal vasodilating substances that feedback to the glomerulus causing hyperfiltration. Hyperfiltration leads to glomerulosclerosis and proteinuria, with eventual reduction in kidney function. The crucial steps of vasodilating substance production and hyperfiltration in children with SCD have not been proven. Treatment of sickle cell nephropathy is aimed at the reduction of proteinuria with angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Hydroxyurea and chronic transfusion therapy may also alter the progression of sickle cell nephropathy in children. Further studies are needed to identify an accurate model and effective treatments for sickle cell nephropathy.
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PMID:Sickle cell nephropathy: challenging the conventional wisdom. 2120 78

We report a case of 15-yr-old child that was presented with headache, polyuria, polydipsia, recent ocular motor and abducens nerve palsies and rapid visual loss. He had a long history of progressive symmetric muscular weakness predominant in the lower limb girdle. Water deprivation revealed central diabetes insipidus. Hormonal explorations demonstrated preserved pituitary function with mild hyperprolactinemia at 21.5 ng/ml (N: 2.6 to 13.1 ng/ml). Magnetic resonance imaging showed an extensive isosignal T1 and hyposignal T2 enhanced lesion infiltrating the pituitary gland, optic-chiasmal hypothalamic region, cavernous sinus, cerebrum tent and sphenoid and temporal meningeal spaces. The serum level of angiotensin converting enzyme and cerebrospinal fluid analysis were normal. No other systemic localisation was identified. Muscle biopsy objectified dystrophic changes. Genetic study identified a delT 521 mutation characteristic of Limb-girdle muscular dystrophy type 2C. Corticotherapy rapidly ameliorated the neurological symptoms. This patient was diagnosed as having neurosarcoidosis. Neurosarcoidosis is rarely reported in childhood. We discuss the problems related to diagnosis in such a situation below.
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PMID:Isolated neurosarcoidosis revealed by diabetes insipidus, visual loss and diplopia in a child patient: a diagnostic problem. 2479 Mar 80

The aim of this study was to evaluate fosinopril-induced changes in hemodynamic parameters and tactile allodynia in a rat model of diabetes. Diabetes was induced by streptozotocin (STZ; 50 mg/kg, i.p.) in male Wistar rats. STZ produced hyperglycemia, weight loss, polydipsia, polyphagia, and polyuria as well as long-term arterial hypotension, bradycardia, and tactile allodynia at 10-12 weeks. Daily administration of the angiotensin converting enzyme inhibitor, fosinopril (25 mg/kg, p.o., for 11 weeks) partially reduced the loss of body weight, decreased hyperglycemia, and systolic blood pressure in diabetic rats. Likewise, systemic administration of fosinopril prevented the development and maintenance of tactile allodynia in STZ-induced diabetic rats. These data suggest that fosinopril may have a role in the pharmacotherapy of diabetic neuropathic pain.
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PMID:Fosinopril Prevents the Development of Tactile Allodynia in a Streptozotocin-Induced Diabetic Rat Model. 2634 82

Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I(131) therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH.
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PMID:Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus. 2765 1


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