Glomerular abnormalities in long-term experimental diabetes. Role of hemodynamic and nonhemodynamic factors and effects of antihypertensive therapy

Abstract

To evaluate the role of glomerular hypertension, glomerular hypertrophy, glomerular lipid deposition, and plasma cholesterol levels in diabetic glomerulopathy, Munich-Wistar rats received streptozocin and daily insulin injections and were assigned to one of three groups: untreated diabetic (DMC), hydralazine-treated diabetic (DMH), and enalapril-treated diabetic (DME). Age-matched control rats were also studied. At 6-10 wk of diabetes, DMC rats showed marked elevations of glomerular pressure and glomerular filtration rate as well as slight glomerular enlargement and cholesterol elevation. DMH and DME rats exhibited arterial hypotension but no change in cholesterol or glomerular volume. Glomerular pressure was normalized by enalapril but not by hydralazine treatment. Additional rats were followed up to 12 mo of diabetes. Slight hypertension was seen in DMC rats, whereas sustained hypotension occurred in DMH and DME rats. Progressive albuminuria occurred in DMC and DMH but not in DME rats. At 12 mo, glomerular hypertension persisted in DMC and DMH rats but was still absent in DME rats. Cholesterol was elevated in DMC and slightly lower in DMH and DME rats. Glomeruli were equally enlarged in the diabetic groups. Glomerular sclerotic lesions and lipid deposits appeared in DMC and DMH but not in DME rats. These findings are consistent with the notion that glomerular hypertension may promote glomerular injury in experimental diabetes. Glomerular lipid deposition may also participate in this process, although a causal relationship was not demonstrated. Glomerular hypertrophy and cholesterol were unrelated to glomerular injury, although they may have exacerbated hemodynamically mediated damage.