J. Thulesen et al., Adrenergic blockade in diabetic and uninephrectomized rats: Effects on renal size and on renal and urinary contents of epidermal growth factor, NEPHRON, 81(2), 1999, pp. 172-182
The present study reports on the effects of adrenergic blocking agents on t
he renal growth and on the renal content and urinary excretion of epidermal
growth factor (EGF) in streptozotocin-induced diabetic or uninephrectomize
d rats. Diabetic and uninephrectomized rats were allocated to groups treate
d with either saline or adrenergic antagonists and compared to controls and
sham-operated controls, respectively. 24-hour urine samples were obtained
on days 7, 14, and 21 and renal tissue samples on day 21. The 24-hour urina
ry excretion of EGF from controls and saline-treated diabetic rats was comp
arable. In adrenergic antagonist treated diabetic rats, it was reduced by a
t feast 40% throughout the study period. Uninephrectomy caused a 50% reduct
ion in the urinary excretion of EGF. This was not influenced by treatment w
ith an adrenergic antagonist. After 3 weeks, saline-treated diabetic rats h
ad an increase of 33% in kidney weight when compared to controls. The adren
ergic antagonist treated diabetic groups had a significantly lower increase
of 15%. Postnephrectomized renal growth was not affected by adrenergic ant
agonists. The total renal content of EGF was comparable in the saline-treat
ed diabetic group and the control group, but was reduced by approximately 5
0% in the kidneys from the adrenergic antagonist treated diabetic groups. R
enal EGF mRNA levels were also reduced in adrenergic antagonist treated dia
betic rats. In contrast to diabetes, the renal growth following nephrectomy
was not affected by adrenergic blocking agents. These results provide evid
ence for fundamental differences between diabetes-related renal growth and
that observed in compensation to nephrectomy and suggest a connection betwe
en adrenergic activity, renal growth, and EGF in diabetes.