Platelet-activating factor receptor antagonist improves renal function and glomerular lesions in renal ablation.
In the renal ablation model hemodynamic changes, glomerular hypertrophy, and the release of inflammatory mediators contribute to structural damage and functional changes. Platelet-activating factor (PAF) has both hemodynamic and immune-mediating properties. We therefore examined the role for a PAF receptor antagonist (WEB 2170) on glomerular hemodynamic function, albuminuria, and structural alterations in a rat model of renal ablation (Nx). WEB 2170 treatment was started 10 weeks after renal ablation, and the variables were assessed at 36 weeks after surgery. WEB 2170 significantly improved inulin and PAH clearances at 36 weeks (inulin clearance: Nx, 182 +/- 28 microliters/min/100 gm body weight; Nx plus WEB, 284 +/- 19 microliters/min/100 gm body weight; p < 0.05; PAH clearance: Nx, 718 +/- 85 microliters/min/100 gm body weight; Nx plus WEB, 1215 +/- 103 microliters/min/100 gm body weight; p < 0.05). Glomerular prostaglandin E2 (PGE2) formation was significantly increased in nephrectomized rats treated with WEB 2170 when compared with nephrectomized animals not treated (PGE2: Nx, 103 +/- 16 pg/min/mg protein; Nx plus WEB, 182 +/- 19 pg/min/mg protein; p < 0.01). The PAF receptor antagonist did not change albuminuria (Nx, 205 +/- 56 mg/24 hr; Nx plus WEB, 178 +/- 48 mg/24 hr). Glomeruli of rats treated with WEB 2170 had significantly fewer sclerotic lesions at 36 weeks when compared with untreated animals (Nx, 36.5 +/- 4.4%; Nx plus WEB, 19.3 +/- 3.7%; p < 0.05). The results demonstrate that a PAF receptor antagonist significantly improves whole kidney clearances and glomerular morphology.(ABSTRACT TRUNCATED AT 250 WORDS)
Thaiss
F
F
Department of Medicine, University Hospital, Hamburg, FRG.
Mihatsch
M J
MJ
Oberle
G
G
Haberstroh
U
U
Brecht
H M
HM
Stahl
R A
RA
D000419:Albuminuria / Q000652:urine; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015777:Eicosanoids / Q000096:biosynthesis; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009392:Nephrectomy / Q000379:methods; D009929:Organ Size / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D001381:Azepines; D015777:Eicosanoids; D010972:Platelet Activating Factor; D014230:Triazoles; D007444:Inulin; C063964:bepafant; D010130:p-Aminohippuric Acid