Nephrol Dial Transplant (2000) 15: 811-817
© 2000 European Renal Association-European Dialysis and Transplant Association
Aminoguanidine induces haematuria of non-glomerular origin in spontaneously hypertensive rats
Department of Medicine, Teikyo University School of Medicine, 2–11–1 Kaga, Itabashiku., Tokyo 173–8605, 1 Teikyo University School of Medicine, Mizonokuchi, Takatsuku, Kawasakisi, 2 Sysmex, Co. Ltd, Kobe and 3 Seirei Hamamatsu Hospital, Department of Internal Medicine, Division of Nephrology, Sumiyoshi, Hamamatsu, Shizuoka, Japan
Background. Administration of NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS), induces glomerulosclerosis in spontaneously hypertensive rats (SHR). We investigated the effects of administering aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS), on glomerular histology, serum creatinine concentration, albuminuria and haematuria in SHR.
Methods. SHR and Wistar Kyoto rats (WKR) (age, 7 weeks) were given a daily water supply with or without 0.1% AG. Every 4 weeks, 24 h urine samples were collected and checked for haematuria by a dipstick method, and systolic blood pressure was measured. After 16 weeks, serum creatinine, albuminuria and glomerulosclerosis indices (GSI) were evaluated, and the size of urinary erythrocytes in AG-treated SHR was measured by flow cytometry. Glomeruli were observed by transmission and scanning electron microscopy. Some AG-treated SHR received a furosemide injection and then urinary erythrocyte size was determined.
Results. Systolic blood pressure, serum creatinine, albuminuria and GSI were similar between the untreated and AG-treated groups in both strains. However, AG treatment induced significant haematuria in SHR, but not in WKR. Electron microscopy did not provide any evidence for glomerular bleeding sites in AG-treated SHR. In urine with osmolalities exceeding 750 mOsm/kg, haematuria of AG-treated SHR consisted of erythrocytes smaller in size than venous erythrocytes. After furosemide injection leading to near isotonic urine, the size of urinary erythrocytes was similar to that of venous erythrocytes.
Conclusions. The absence of morphological evidence for glomerular bleeding sites and similar intrinsic size between urinary and venous erythrocytes suggest that AG induces a non-glomerular type of haematuria in SHR.
Keywords: aminoguanidine; flow cytometry; haematuria; spontaneously hypertensive rats
Correspondence and offprint requests to: Mitsumasa Nagase MD, Department of Medicine, Teikyo University School of Medicine, 2–11–1, Kaga, Itabashiku, Tokyo 173–8605, Japan.