Studies of glomerular protein content in the diabetic hypertensive rat: the effect of antihypertensive therapy

Abstract

The effects of enalapril and verapamil on glomerular protein content, fractional mesangial area and glomerular basement membrane (GBM) thickness were examined in spontaneously hypertensive rats with streptozotocin-induced diabetes. Two groups of 16 animals received enalapril maleate or verapamil to achieve normal blood pressure while a third untreated group remained hypertensive throughout the 3 month experimental period. Blood glucose levels were maintained at 6-10 mmol/L in each group. 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 I1 (AII) and glomerular A11 receptors were also quantitated at the end of the experiment. At 3 months, proteinuria was lowest in the enalapril-treated animals while creatinine clearance was lower in the treated groups than controls. Glomerular protein content (pg/glomerulus) was lower in the enalapril-treated group than verapamiltreated (P< 0.01) or untreated rats (P< 0.05). Kidney weight, GBM thickness and fractional mesangial area were also lowest in this group (P< 0.001 compared to other groups). Glomerular A11 receptor number was comparable among groups when expressed as sites/glomerulus. The data suggest that enalapril reduces glomerular protein content independently of blood pressure control and that this effect corresponds with changes in mesangial area and GBM thickness.