The effect of dilazep, an adenosine potentiator and platelet aggregati
on inhibitor, on experimental diabetic nephropathy was investigated in
spontaneous diabetic Chinese hamster. Prediabetic animals, 8 weeks of
age, were divided into two groups. In one group, 5 mg/kg dilazep was
injected i.p. once a day. In the other group, saline of the same amoun
t was injected. Age- and sex-matched animals from a nondiabetic sublin
e were used as controls. No difference was observed in body weight, me
an blood pressure, fasting plasma glucose and glycated hemoglobin leve
l between diabetic animals with and without dilazep administration thr
oughout the entire period of experiment. Urinary protein excretions in
untreated diabetic animals increased significantly compared to those
of nondiabetic controls at 8 weeks (17.5 +/- 3.5 vs 2.0 +/- 0.1 mg/day
), and at 24 weeks (25.3 +/- 5.1 vs 2.7 +/- 0.1 mg/day) of experiment.
In diabetic animals with dilazep treatment, urinary protein excretion
s (4.1 +/- 0.7 at 8 weeks and 13.1 +/- 2.9 mg/day at 24 weeks of exper
iment) were significantly suppressed compared to those in untreated di
abetic animals. Significant thickening of glomerular basement membrane
(GBM) was observed in diabetic animals both with and without dilazep
administration at 24 weeks of experiment compared to that in nondiabet
ic controls. The number of anionic sites in GBM, stained by polyethyle
neimine, was reduced in untreated diabetic animals, but was not differ
ent in dilazep treated animals compared to that in nondiabetic control
s. It was concluded that dilazep administration suppressed urinary pro
tein excretion in diabetic Chinese hamster possibly through the preser
vation of charge barrier of the glomerulus.