RENOPROTECTIVE DIFFERENCES BETWEEN PERINDOPRIL AND ENALAPRIL IN THE DIABETIC HYPERTENSIVE RAT DO NOT REFLECT GLOMERULAR ANGIOTENSIN-CONVERTING ENZYME-ACTIVITY

1. The various angiotensin-converting enzyme inhibitors have structura l differences which affect their affinities for the catalytic sites on converting enzyme. We postulated that such differences might result i n differences in renoprotective efficacy. We investigated this in the diabetic spontaneous hypertensive rat. We also investigated whether th ese differences might reflect variations in glomerular or plasma angio tensin-converting enzyme activity. 2. One week after induction of diab etes, rats were started on antihypertensive therapy: enalapril, 10 mg. day(-1).kg(-1), or perindopril, 4 mg.day(-1).kg(-1), in the drinking w ater. After 3 months, the rats were killed, blood samples were taken a nd tissues were harvested. Angiotensin-converting enzyme activity in i solated glomeruli and plasma was measured by fluorimetric assay, Glome rular protein content was also determined. 3. Urinary protein excretio n was significantly lower in perindopril-treated rats than in either c ontrols (P < 0.0005) or enalapril-treated rats (P < 0.05), Glomerular protein content was also lower in perindopril-treated rats (P < 0.05 v ersus enalapril; P < 0.005 versus control), There was no difference in glomerular angiotensin-converting enzyme activity between the two inh ibitors although both were lower than control values (enalapril P < 0. 025; perindopril P < 0.025), Plasma angiotensin-converting enzyme acti vity was significantly lower in the perindopril group than in either c ontrol (P < 0.005) or the enalapril group (P < 0.01). 4. We conclude t hat in the spontaneous hypertensive rat with streptozotocin-induced di abetes, perindopril is more effective than enalapril in reducing prote inuria and glomerular protein accumulation. This difference does not r esult from differences in glomerular-converting enzyme activity.