Doxazosin prevents proteinuria and glomerular loss of heparan sulfate in diabetic rats.
We examined whether blood pressure reduction or good glycemic control equally lower albuminuria by preventing glomerular loss of heparan sulfate and progression of glomerulosclerosis in streptozotocin-induced diabetic rats. We used doxazosin, and alpha 1-adrenergic blocker, to lower systemic blood pressure, and good glycemic control was achieved by insulin treatment. Rats were killed after 20 weeks of treatment. Doxazosin significantly lowered systolic pressure in diabetic rats; however, it had no effect in normal rats. Good glycemic control also lowered systolic pressure. In diabetic rats with good glycemic control, doxazosin had an additive effect on blood pressure. Glomerular heparan sulfate synthesis was significantly lower and urinary albumin excretion higher in diabetic than in normal rats. Both doxazosin treatment and good glycemic control normalized these abnormalities in diabetic rats. Insulin normalized plasma glucose and glycosylated HbA1 concentrations in diabetic rats, as did doxazosin. Significant increases in mesangial area and glomeruloscelerosis were observed in diabetic rats. Only good glycemic control normalized these pathological changes in all diabetic rats. Two-way factorial ANOVA showed an interaction between the effects 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. Conversely, good glycemic control prevented all three of the preceding sequelae.
Jyothirmayi
G N
GN
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA.
Alluru
I
I
Reddi
A S
AS
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000419:Albuminuria; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000473:pathology; D017292:Doxazosin / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology / Q000473:pathology; D006497:Heparan Sulfate / Q000378:metabolism*; D015994:Incidence; D007328:Insulin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013599:Systole
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D017292:Doxazosin; D006497:Heparan Sulfate; D007328:Insulin