Angiotensin-Converting Enzyme Inhibition Partially Prevents Diabetic Organomegaly

Melkon Hajinazarian, Fernando G. Cosio, Norris Stanley Nahman, John D. Mahan, Cynthia McAllister

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)105-117
Number of pages13
JournalAmerican Journal of Kidney Diseases
Volume23
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Keywords

  • Diabetes
  • angiotensin
  • hypertrophy
  • nephropathy
  • organomegaly

ASJC Scopus subject areas

  • Nephrology

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