The effects of perindopril and triple therapy in a normotensive model of diabetic nephropathy

• Published in: Diabetes (New York, N.Y.) Vol. 42; no. 4; pp. 604 - 609
• Main Authors: O'BRIEN, R. C, COPPER, M. E, JERUMS, G, DOYLE, A. E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-04-1993
• Subjects: ACE inhibitors; Analysis of Variance; Angiotensin converting enzyme inhibitors; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Antihypertensive agents; Biological and medical sciences; Blood Glucose - metabolism; Blood Pressure - drug effects; Body Weight - drug effects; Cardiovascular system; Development and progression; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - physiopathology; Diabetic nephropathies; Diabetic Nephropathies - blood; Diabetic Nephropathies - drug therapy; Drug therapy; Drug Therapy, Combination; Evaluation; Glomerular Filtration Rate; Glomerular Mesangium - drug effects; Glomerular Mesangium - pathology; Hydralazine - therapeutic use; Hydrochlorothiazide - therapeutic use; Hypertension; Indoles - therapeutic use; Kidney Glomerulus - drug effects; Kidney Glomerulus - pathology; Male; Medical sciences; Perindopril; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Reserpine - therapeutic use; Endocrinopathy; Drug combination; Urinary system disease; Rat; Enzyme; Diabetes mellitus; Rodentia; Enzyme inhibitor; Renal disease; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Nephropathy; Treatment; Peptidyl-dipeptidase A; Animal; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; Complication; Proteinases; Streptozotocin; Comparative study
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.42.4.604

The effect of the angiotensin-converting enzyme inhibitor, perindopril, on functional and structural parameters of diabetic nephropathy has been compared with triple therapy (hydralazine, reserpine, and hydrochlorothiazide) in normotensive, STZ-induced diabetic Sprague-Dawley rats. Animal groups included control rats, diabetic rats treated with perindopril, diabetic rats receiving triple therapy, and untreated diabetic rats. Treatment was continued for 32 wk. Blood pressure reduction and severity of diabetes, as assessed by body weight and glycemic control were similar with both drug regimens. A similar rise in plasma renin activity occurred in the two groups receiving antihypertensive drugs, whereas the perindopril but not the triple therapy group had suppressed plasma angiotensin-converting enzyme activity. No significant difference was observed in renal function among the four groups. Diabetes was associated with a progressive increase in albuminuria, but this rise was ameliorated by both perindopril and triple therapy. No significant difference was noted in albuminuria between triple therapy and perindopril-treated diabetic rats. Diabetes was associated with glomerular basement membrane thickening, mesangial expansion, and glomerular volume. No glomerular ultrastructural parameter was affected by antihypertensive drugs. No specific benefit of angiotensin-converting enzyme inhibition over triple therapy could be detected in this normotensive model of diabetic nephropathy.