Aminoguanidine induces haematuria of non-glomerular origin in spontaneously hypertensive rats.
BACKGROUND
Administration of N(G)-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.
Arai
T
T
Department of Medicine, Teikyo University School of Medicine, 2-11-1 Tokyo, Japan.
Morimoto
K
K
Oka
M
M
Hikita
T
T
Arai
K
K
Umezawa
K
K
Nagase
M
M
Yamamoto
T
T
D000419:Albuminuria / Q000139:chemically induced; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005921:Glomerulonephritis / Q000473:pathology; D006146:Guanidines / Q000633:toxicity*; D006417:Hematuria / Q000139:chemically induced* / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole / Q000187:drug effects
D006146:Guanidines; D003404:Creatinine; C004479:pimagedine