STUDIES OF GLOMERULAR PROTEIN-CONTENT IN THE DIABETIC HYPERTENSIVE RAT - THE EFFECT OF ANTIHYPERTENSIVE THERAPY

The effects of enalapril and verapamil on glomerular protein content, fractional mesangial area and glomerular basement membrane (GEM) thick ness were examined in spontaneously hypertensive rats with streptozoto cin-induced diabetes. Two groups of 16 animals received enalapril male ate or verapamil to achieve normal blood pressure while a third untrea ted group remained hypertensive throughout the 3 month experimental pe riod. Blood glucose levels were maintained at 6-10 mmol/L in each grou p. Creatinine clearance and 24 h urine protein were measured at second weekly intervals. Glomerular protein and other structural parameters were measured at the end of the experiment. Plasma angiotensin II (AII ) and glomerular AII receptors were also quantitated at the end of the experiment. At 3 months, proteinuria was lowest in the enalapril-trea ted animals while creatinine clearance was lower in the treated groups than controls. Glomerular protein content (mu g/glomerulus) was lower in the enalapril-treated group than verapamil-treated (P < 0.01) or u ntreated rats (P < 0.05). Kidney weight, GEM thickness and fractional mesangial area were also lowest in this group (P < 0.001 compared to o ther groups). Glomerular AII receptor number was comparable among grou ps when expressed as sites/glomerulus. The data suggest that enalapril reduces glomerular protein content independently of blood pressure co ntrol and that this effect corresponds with changes in mesangial area and GEM thickness.