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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1996-11-20
pubmed:abstractText
TCV-116 and enalapril were given in two stages: (early phase) for 6 to 10 weeks to 5/6 nephrectomized (NX) rats two weeks after nephrectomy, 12-week-old Wistar fatty (WF) rats and 7-week-old spontaneously hypercholesterolemic (SHC) rats; and (late phase) for 6 to 16 weeks to 5/6 NX rats 11 weeks after nephrectomy, 27-week-old WF rats and 10-week-old SHC rats. Urinary albumin, blood pressure (BP), glomerular filtration rate (GFR) and renal histology were examined. In the early phase, both agents inhibited proteinuria and tended to inhibit glomerulosclerosis. TCV-116 also inhibited interstitial inflammation. The antiproteinuric effects did not necessarily correlate with the BP-lowering effects. In the late phase, both agents showed equal antiproteinuric and antihypertensive effects. In 5/6NX and WF rats, TCV-116 inhibited tubulointerstitial inflammation/fibrosis, glomerulosclerosis and renal dysfunction, but enalapril had little effect on these parameters. In the SHC rats, TCV-116 inhibited renal tubulointerstitial inflammation and glomerulosclerosis, but enalapril inhibited only glomerulosclerosis. After drug administration, there was a positive correlation between proteinuria and BP, and a negative correlation between the severity of tissue damage and GFR, but not BP. These findings suggest that initial BP-independent tubulointerstitial inflammation may enhance glomerulosclerosis in the late phase, and TCV-116 might prevent the development of glomerulosclerosis through inhibition of angiotensin II-mediated tubulointerstitial damage in these models.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0098-6577
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S115-8
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:8743529-Angiotensin-Converting Enzyme Inhibitors, pubmed-meshheading:8743529-Animals, pubmed-meshheading:8743529-Antihypertensive Agents, pubmed-meshheading:8743529-Benzimidazoles, pubmed-meshheading:8743529-Biphenyl Compounds, pubmed-meshheading:8743529-Blood Pressure, pubmed-meshheading:8743529-Diabetes Mellitus, Type 2, pubmed-meshheading:8743529-Enalapril, pubmed-meshheading:8743529-Glomerular Filtration Rate, pubmed-meshheading:8743529-Glomerulonephritis, pubmed-meshheading:8743529-Hypercholesterolemia, pubmed-meshheading:8743529-Kidney Glomerulus, pubmed-meshheading:8743529-Nephritis, Interstitial, pubmed-meshheading:8743529-Prodrugs, pubmed-meshheading:8743529-Proteinuria, pubmed-meshheading:8743529-Rats, pubmed-meshheading:8743529-Rats, Wistar, pubmed-meshheading:8743529-Tetrazoles
pubmed:year
1996
pubmed:articleTitle
TCV-116 inhibits renal interstitial and glomerular injury in glomerulosclerotic rats.
pubmed:affiliation
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
pubmed:publicationType
Journal Article