DOXAZOSIN PREVENTS PROTEINURIA AND GLOMERULAR LOSS OF HEPARAN-SULFATEIN DIABETIC RATS

We examined whether blood pressure reduction or good glycemic control equally lower albuminuria by preventing glomerular loss of heparan sul fate and progression of glomerulosclerosis in streptozotocin-induced d iabetic rats. We used doxazosin, an alpha(1)-adrenergic blocker, to lo wer systemic blood pressure, and good glycemic control was achieved by insulin treatment. Rats were killed after 20 weeks of treatment. Doxa zosin significantly lowered systolic pressure in diabetic rats; howeve r, it had no effect in normal rats. Good glycemic control also lowered systolic pressure. In diabetic rats with good glycemic control, doxaz osin had an additive effect on blood pressure. Glomerular heparan sulf ate synthesis was significantly lower and urinary albumin excretion hi gher in diabetic than in normal rats. Both doxazosin treatment and goo d glycemic control normalized these abnormalities in diabetic rats. In sulin normalized plasma glucose and glycosylated HbA(1) concentrations in diabetic rats, as did doxazosin. Significant increases in mesangia l area and glomerulosclerosis were observed in diabetic rats. Only goo d glycemic control normalized these pathological changes in all diabet ic rats. Two-way factorial ANOVA showed an interaction between the eff ects of doxazosin and insulin on systolic pressure and plasma glucose. The data show that after 20 weeks of doxazosin treatment, albuminuria was reduced by 80%; however, this treatment had no significant effect on mesangial expansion or progression to glomerulosclerosis. Converse ly, good glycemic control pre vented all three of the preceding sequel ae.