TY - JOUR
T1 - Angiotensin-Converting Enzyme Inhibition Partially Prevents Diabetic Organomegaly
AU - Hajinazarian, Melkon
AU - Cosio, Fernando G.
AU - Nahman, N. Stanley
AU - Mahan, John D.
AU - McAllister, Cynthia
N1 - Funding Information:
From the Departments oj Internal Jdedicine. Pathology. and Pediatrics. Ohio State University. Columbus. OH. Received February 23. 1993; accepted in revisedJorm August 30. 1993. Supported by National Institutes oj Health Grant No. DK 433886. Presented in abstract .form at the 25th annual meeting oj the American Society oJNephrology. Baltimore. MD. November 1992. Address reprint requests to Fernando G. Cosio. MD. Department oj Internal Medicine, Nephrology. The Ohio State University. 1654 Upham Dr. Room N21O, Columbus, OH 43210-1228. © 1994 by the National Kidney Foundation. Inc. 0272-6386/94/]]01-0015$3.00/0
PY - 1994
Y1 - 1994
N2 - The present study was conducted to evaluate whether captopril prevents the organomegaly and accumulation of matrix proteins that normally accompanies the diabetic state. The following groups of rats were studied: normal rats, normal rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats, and diabetic rats treated with captopril. All rats were killed at 10 weeks for histologic and morphometric evaluation of tissues. Compared with the normal rats, the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and cardiomegaly, and the increase in organ size was directly related to increasing levels of protein glycosylation. The development of organomegaly was partially prevented by captopril. We determined by morphometry that the hepatomegaly seen in the diabetic rats was due to an increase in cell size and number, while the nephromegaly seen in the diabetic rats was due to an increase in tubular and glomerular cell size and is associated with glomerular hypertrophy. Captopril prevented the development of hepatic and renal cell hypertrophy and glomerular hypertrophy. These effects of captopril were not associated with detectable changes in body weight or levels of glucose, protein glycosylation, glycosuria, or renal histologic changes secondary to glycosuria. The diabetic rats demonstrated significant glomerular mesangial matrix expansion, and captopril treatment partially prevented that expansion. In conclusion, captopril prevents, in part, the development of organomegaly in diabetic rats, and this effect is due mainly to the prevention of the development of cellular hypertrophy. The present findings are most consistent with a direct effect of captopril on cell metabolism during diabetes mellitus.
AB - The present study was conducted to evaluate whether captopril prevents the organomegaly and accumulation of matrix proteins that normally accompanies the diabetic state. The following groups of rats were studied: normal rats, normal rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats, and diabetic rats treated with captopril. All rats were killed at 10 weeks for histologic and morphometric evaluation of tissues. Compared with the normal rats, the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and cardiomegaly, and the increase in organ size was directly related to increasing levels of protein glycosylation. The development of organomegaly was partially prevented by captopril. We determined by morphometry that the hepatomegaly seen in the diabetic rats was due to an increase in cell size and number, while the nephromegaly seen in the diabetic rats was due to an increase in tubular and glomerular cell size and is associated with glomerular hypertrophy. Captopril prevented the development of hepatic and renal cell hypertrophy and glomerular hypertrophy. These effects of captopril were not associated with detectable changes in body weight or levels of glucose, protein glycosylation, glycosuria, or renal histologic changes secondary to glycosuria. The diabetic rats demonstrated significant glomerular mesangial matrix expansion, and captopril treatment partially prevented that expansion. In conclusion, captopril prevents, in part, the development of organomegaly in diabetic rats, and this effect is due mainly to the prevention of the development of cellular hypertrophy. The present findings are most consistent with a direct effect of captopril on cell metabolism during diabetes mellitus.
KW - Diabetes
KW - angiotensin
KW - hypertrophy
KW - nephropathy
KW - organomegaly
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U2 - 10.1016/S0272-6386(12)80819-5
DO - 10.1016/S0272-6386(12)80819-5
M3 - Article
C2 - 8285184
AN - SCOPUS:0028044716
SN - 0272-6386
VL - 23
SP - 105
EP - 117
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 1
ER -