Antihypertensive therapy in a model combining spontaneous hypertension with diabetes.

Abstract

We have compared the effects of the angiotensin converting enzyme inhibitor, perindopril, and a conventional antihypertensive regimen (triple therapy: hydralazine, reserpine and hydrochlorothiazide) on kidney function and albuminuria in hypertensive diabetic rats. Diabetes was induced with streptozotocin in spontaneously hypertensive (SHR) rats and they were randomized to receive no treatment, perindopril or triple therapy. Antihypertensive drugs were commenced at the time of induction of diabetes and continued for 16 weeks. Blood pressure reduction was equal in the groups treated with perindopril or triple therapy. All groups had similar severity of diabetes as determined by body weight, serum glucose and glycated hemoglobin levels. Whereas plasma renin activity rose in both the perindopril and triple therapy groups, it is likely that the effects on angiotensin II levels were opposite since perindopril but not triple therapy was associated with a significant reduction in plasma angiotensin converting enzyme activity. Diabetes was associated with an increase in glomerular filtration rate. At 12 weeks, glomerular filtration rate was higher in the perindopril treated group when compared to the triple therapy group, but neither group treated with antihypertensive therapy was different to untreated diabetic rats. Both drug regimens reduced albuminuria in the diabetic rats to a similar degree apparently independently of their effects on the renin-angiotensin system. Studies in diabetic subjects are warranted to evaluate different classes of antihypertensive drugs with respect to their effects on kidney function, proteinuria and glomerular morphology.