Inhibition of angiotensin-converting enzyme reduces urinary albumin excretion but not regional albumin clearance in experimental diabetes.
Albuminuria and increased regional albumin clearance are known to develop concomitantly in diabetes. The anti-proteinuric effect of angiotensin-converting enzyme inhibitor therapy is well established. We studied whether angiotensin-converting enzyme inhibitor therapy with perindoprilat in comparison with conventional antihypertensive treatment could influence the development of increased regional albumin clearance as well as albuminuria in experimental diabetes. Rats with streptozotocin-induced diabetes were randomized into a saline group (n = 7), a perindoprilat (1 mg/kg per day) group (n = 8), and a hydralazine (3 mg/kg per day) group (n = 6); six rats served as non-diabetic controls. After 6-8 weeks, blood pressure was equally reduced in the perindoprilat- and hydralazine-treated groups (P < 0.01). Twenty-four-hour urinary protein and albumin excretion were increased in diabetic rats compared to control rats (P < 0.001). Hydralazine did not reduce 24 h protein or albumin excretion, whereas perindoprilat treatment reduced both (P < 0.001) to levels comparable to those of control rats. Regional albumin clearance, assessed in the eye, ileum, lung, skeletal muscle and skin, was clearly elevated in diabetic rats compared to control rats; however, neither drug therapy had an effect on albumin clearance.
Huijberts
M
M
Department of Internal Medicine, University Hospital Maastricht, Netherlands.
Wolffenbuttel
B
B
Crijns
F
F
Kruseman
A N
AN
Bemelmans
M
M
Van Essen
H
H
Smits
J
J
Boudier
H S
HS
D000418:Albumins / Q000378:metabolism*; D000419:Albuminuria / Q000188:drug therapy* / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000652:urine; D006830:Hydralazine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000418:Albumins; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D006830:Hydralazine; C053500:perindoprilat