title: Temocapril, a long-acting non-SH group angiotensin converting enzyme inhibitor, modulates glomerular injury in chronic puromycin aminonucleoside nephrosis.
abstract: The purpose of the present study was to determine whether chronic administration of temocapril, a long-acting non-SH group angiotensin converting enzyme (ACE) inhibitor, reduced proteinuria, inhibited glomerular hypertrophy and prevented glomerulosclerosis in chronic puromycin aminonucleoside (PAN) - induced nephrotic rats. Nephrosis was induced by injection of PAN (15mg/100g body weight) in male Sprague-Dawley (SD) rats. Four groups were used, i) the PAN group (14), ii) PAN/temocapril (13), iii) temocapril (14) and iv) untreated controls (15). Temocapril (8 mg/kg/day) was administered to the rats which were killed at weeks 4, 14 or 20. At each time point, systolic blood pressure (BP), urinary protein excretion and renal histopathological findings were evaluated, and morphometric image analysis was done. Systolic BP in the PAN group was significantly high at 4, 14 and 20 weeks, but was normal in the PAN/temocapril group. Urinary protein excretion in the PAN group increased significantly, peaking at 8 days, then decreased at 4 weeks, but rose again significantly at 14 and 20 weeks. Temocapril did not attenuate proteinuria at 8 days, but it did markedly lower it from weeks 4 to 20. The glomerulosclerosis index (GSI) was 6.21 % at 4 weeks and respectively 25.35 % and 30.49 % at 14 and 20 weeks in the PAN group. There was a significant correlation between urinary protein excretion and GSI (r = 0.808, p < 0.0001). The ratio of glomerular tuft area to the area of Bowman's capsules (GT/BC) in the PAN group was significantly increased, but it was significantly lower in the PAN/temocapril group. It appears that temocapril was effective in retarding renal progression and protected renal function in PAN neprotic rats.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zheng
authors.forename: Isao
authors.initials: I
authors.lastname: Shirato
authors.forename: Atsuko
authors.initials: A
authors.lastname: Maeda
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Jie
authors.initials: J
authors.lastname: Liao
authors.forename: Ichiyu
authors.initials: I
authors.lastname: Shou
authors.forename: Mitsumine
authors.initials: M
authors.lastname: Fukui
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control; D008297:Male; D023421:Models, Animal; D009401:Nephrosis / Q000139:chemically induced / Q000188:drug therapy*; D011507:Proteinuria / Q000139:chemically induced / Q000517:prevention & control*; D011692:Puromycin Aminonucleoside; D051381:Rats; D017207:Rats, Sprague-Dawley; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; D011692:Puromycin Aminonucleoside; C055603:temocapril hydrochloride