Antinephritic effects of PGE1 and thiaprostaglandin E1, TEI-5178 and TEI-6122, on crescentic-type anti-GBM nephritis in rats.
The antinephritic effects of PGE1, TEI-5178 and TEI-6122 on crescentic-type anti-glomerular basement membrane (GBM) nephritis in rats were investigated. The test compounds were subcutaneously administered every day for 39 days after the injection of anti-GBM serum. PGE1 (2.0 mg/kg/day), TEI-5178 (0.25 or 0.5 mg/kg/day) and TEI-6122 (0.25 or 0.5 mg/kg/day) significantly reduced urinary protein by 30 to 50% of that of the control at the late stage of nephritis. These test compounds also suppressed the increase of blood urea nitrogen and the development of alteration in the glomeruli by the 40th day. Both TEI-5178 (0.5 mg/kg/day) and TEI-6122 (0.5 mg/kg/day) significantly suppressed the production of antibody to rabbit gamma-globulin in nephritic rats. This was not the case with PGE1, however. In additional experiments to clarify the antinephritic mechanisms of the test compounds, it was found that 15 min after one subcutaneous injection of PGE1 (1.0 mg/kg), TEI-5178 (0.5 mg/kg) or TEI-6122 (0.5 mg/kg), systolic blood pressure in the nephritic rats was transiently reduced by 50 to 60%. On the other hand, these test compounds augmented renal blood flow (20-50%) from 45 min after the injection. The relationship between the antinephritic effect and these subsequent findings will be discussed.
Nagamatsu
T
T
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Kojima
J
J
Ito
M
M
Kondo
N
N
Suzuki
Y
Y
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies; D000917:Antibody Formation / Q000187:drug effects; D001323:Autoantibodies; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
D000906:Antibodies; D001323:Autoantibodies; C051951:antiglomerular basement membrane antibody; C051203:15-cyclohexyl-omega-pentanor-7-thiaprostaglandin E1; C054546:TFC 612; D000527:Alprostadil