Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1981 Feb;102(2):219–228.

Hypertensive-diabetic cardiomyopathy in the rat: an experimental model of human disease.

S M Factor, R Bhan, T Minase, H Wolinsky, E H Sonnenblick
PMCID: PMC1903683  PMID: 7468768

Abstract

The authors recently described a group of diabetic patients with severe congestive heart failure, hypertension, and minimal coronary artery disease, who had significant myocardial degeneration apparently secondary to the combined effects of high blood pressure and diabetes on the heart. To evaluate the effects of hypertension and diabetes mellitus more fully, the authors studied four groups of rats with either no disease, streptozotocin-induced diabetes mellitus, renovascular hypertension, or a combination of hypertension and diabetes. They employed semiquantitative light microscopy, which revealed significantly greater replacement fibrosis in the hypertensive-diabetic rats when compared with the other three groups. Interstitial fibrosis was increased in the hypertensive-diabetic animals, though it was just below the 5% level of significance when compared with the hypertensives. Further analysis, however, revealed that those hypertensive-diabetic animals with the greatest relative cardiac hypertrophy, as measured by the heart weight/body weight ratio, had significantly increased interstitial fibrosis. Surprisingly, diabetes mellitus alone produced no morphologic light-microscopic alterations; yet 8 weeks of combined hypertension and diabetes mellitus led to myocardial degeneration similar to the human disease. These changes do not appear to be secondary to abnormalities of intramyocardial muscular vessels. Measurement of 3 parameters of vascular disease revealed that hypertensive animals with less myocardial damage had greater vascular changes than the more severely affected hypertensive-diabetics. This study provides evidence that the combination of diabetes mellitus and hypertension produces significantly greater myocardial lesions than either disease alone. The similarity of the lesions with those observed in human patients suggests that the hypertensive-diabetic rat is a useful model for elucidating the pathogenesis of clinical myocardial disease in patients with hypertension and diabetes mellitus.

Full text

PDF

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson K. R., Sutton M. G., Lie J. T. Histopathological types of cardiac fibrosis in myocardial disease. J Pathol. 1979 Jun;128(2):79–85. doi: 10.1002/path.1711280205. [DOI] [PubMed] [Google Scholar]
  2. BALME H. W., COLE L. The heredity of hypertension in diabetes mellitus. Q J Med. 1951 Oct;20(80):335–351. [PubMed] [Google Scholar]
  3. Christlieb A. R. Diabetes and hypertensive vascular disease. Mechanisms and treatment. Am J Cardiol. 1973 Sep 20;32(4):592–606. doi: 10.1016/s0002-9149(73)80051-7. [DOI] [PubMed] [Google Scholar]
  4. Christlieb A. R., Kaldany A., D'Elia J. A. Plasma renin activity and hypertension in diabetes mellitus. Diabetes. 1976 Oct;25(10):969–974. doi: 10.2337/diab.25.10.969. [DOI] [PubMed] [Google Scholar]
  5. Craighead J. E. Current views on the etiology of insulin-dependent diabetes mellitus. N Engl J Med. 1978 Dec 28;299(26):1439–1445. doi: 10.1056/NEJM197812282992605. [DOI] [PubMed] [Google Scholar]
  6. D'Elia J. A., Weinrauch L. A., Healy R. W., Libertino J. A., Bradley R. F., Leland O. S., Jr Myocardial dysfunction without coronary artery disease in diabetic renal failure. Am J Cardiol. 1979 Feb;43(2):193–199. doi: 10.1016/s0002-9149(79)80004-1. [DOI] [PubMed] [Google Scholar]
  7. FREEDMAN P., MOULTON R., SPENCER A. G. Hypertension and diabetes mellitus. Q J Med. 1958 Apr;27(106):293–305. [PubMed] [Google Scholar]
  8. Factor S. M., Minase T., Sonnenblick E. H. Clinical and morphological features of human hypertensive-diabetic cardiomyopathy. Am Heart J. 1980 Apr;99(4):446–458. doi: 10.1016/0002-8703(80)90379-8. [DOI] [PubMed] [Google Scholar]
  9. Factor S. M., Okun E. M., Minase T. Capillary microaneurysms in the human diabetic heart. N Engl J Med. 1980 Feb 14;302(7):384–388. doi: 10.1056/NEJM198002143020706. [DOI] [PubMed] [Google Scholar]
  10. Feuvray D., Idell-Wenger J. A., Neely J. R. Effects of ischemia on rat myocardial function and metabolism in diabetes. Circ Res. 1979 Mar;44(3):322–329. doi: 10.1161/01.res.44.3.322. [DOI] [PubMed] [Google Scholar]
  11. GELLMAN D. D., PIRANI C. L., SOOTHILL J. F., MUEHRCKE R. C., KARK R. M. Diabetic nephropathy: a clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 1959 Dec;38:321–367. [PubMed] [Google Scholar]
  12. Gay A. J., Rosenbaum A. L. Retinal artery pressure in asymmetric diabetic retinopathy. Arch Ophthalmol. 1966 Jun;75(6):758–762. doi: 10.1001/archopht.1966.00970050760008. [DOI] [PubMed] [Google Scholar]
  13. Giacomelli F., Wiener J. Primary myocardial disease in the diabetic mouse. An ultrastructural study. Lab Invest. 1979 Apr;40(4):460–473. [PubMed] [Google Scholar]
  14. Haider B., Ahmed S. S., Moschos C. B., Oldewurtel H. A., Regan T. J. Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes. Circ Res. 1977 Jun;40(6):577–583. doi: 10.1161/01.res.40.6.577. [DOI] [PubMed] [Google Scholar]
  15. Hamby R. I., Zoneraich S., Sherman L. Diabetic cardiomyopathy. JAMA. 1974 Sep 23;229(13):1749–1754. [PubMed] [Google Scholar]
  16. Kannel W. B., Hjortland M., Castelli W. P. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29–34. doi: 10.1016/0002-9149(74)90089-7. [DOI] [PubMed] [Google Scholar]
  17. Ledet T. Diabetic cardiopathy. Quantitative histological studies of the heart from young juvenile diabetics. Acta Pathol Microbiol Scand A. 1976 Sep;84(5):421–428. [PubMed] [Google Scholar]
  18. Ledet T. Histological and histochemical changes in the coronary arteries of old diabetic patients. Diabetologia. 1968 Nov;4(5):268–272. doi: 10.1007/BF01309899. [DOI] [PubMed] [Google Scholar]
  19. Mauer S. M., Steffes M. W., Azar S., Sandberg S. K., Brown D. M. The effects of Goldblatt hypertension on development of the glomerular lesions of diabetes mellitus in the rat. Diabetes. 1978 Jul;27(7):738–744. doi: 10.2337/diab.27.7.738. [DOI] [PubMed] [Google Scholar]
  20. McMillan D. E. Diabetic angiopathy--its lessons in vascular physiology. Am Heart J. 1978 Sep;96(3):401–406. doi: 10.1016/0002-8703(78)90053-4. [DOI] [PubMed] [Google Scholar]
  21. Mogensen C. E. High blood pressure as a factor in the progression of diabetic nephropathy. Acta Med Scand Suppl. 1976;602:29–32. doi: 10.1111/j.0954-6820.1977.tb07638.x. [DOI] [PubMed] [Google Scholar]
  22. Mogensen C. E. Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment. Scand J Clin Lab Invest. 1976 Jul;36(4):383–388. doi: 10.1080/00365517609055274. [DOI] [PubMed] [Google Scholar]
  23. Oakley W. G., Pyke D. A., Tattersall R. B., Watkins P. J. Long-term diabetes. A clinical study of 92 patients after 40 years. Q J Med. 1974 Jan;43(169):145–156. [PubMed] [Google Scholar]
  24. Pell S., D'Alonzo C. A. Some aspects of hypertension in diabetes mellitus. JAMA. 1967 Oct 2;202(1):104–110. doi: 10.1001/jama.202.1.104. [DOI] [PubMed] [Google Scholar]
  25. Regan T. J., Ahmed S. S., Levinson G. E., Oldewurtel H. A., Ahmad M. R., Haider B., Lyons M. M. Cardiomyopathy and regional scar in diabetes mellitus. Trans Assoc Am Physicians. 1975;88:217–223. [PubMed] [Google Scholar]
  26. Regan T. J., Lyons M. M., Ahmed S. S., Levinson G. E., Oldewurtel H. A., Ahmad M. R., Haider B. Evidence for cardiomyopathy in familial diabetes mellitus. J Clin Invest. 1977 Oct;60(4):884–899. doi: 10.1172/JCI108843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Regan T. J., Weisse A. B. The question of cardiomyopathy in diabetes mellitus. Ann Intern Med. 1978 Dec;89(6):1000–1002. doi: 10.7326/0003-4819-89-6-1000. [DOI] [PubMed] [Google Scholar]
  28. Rubler S., Dlugash J., Yuceoglu Y. Z., Kumral T., Branwood A. W., Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972 Nov 8;30(6):595–602. doi: 10.1016/0002-9149(72)90595-4. [DOI] [PubMed] [Google Scholar]
  29. Seneviratne B. I. Diabetic cardiomyopathy: the preclinical phase. Br Med J. 1977 Jun 4;1(6074):1444–1446. doi: 10.1136/bmj.1.6074.1444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sohar E., Ravid M., Ben-Shaul Y., Reshef T., Gafni J. Diabetic fibrillosis. A report of three cases. Am J Med. 1970 Jul;49(1):64–69. doi: 10.1016/s0002-9343(70)80114-0. [DOI] [PubMed] [Google Scholar]
  31. Vracko R., Benditt E. P. Basal lamina: the scaffold for orderly cell replacement. Observations on regeneration of injured skeletal muscle fibers and capillaries. J Cell Biol. 1972 Nov;55(2):406–419. doi: 10.1083/jcb.55.2.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vracko R., Benditt E. P. Capillary basal lamina thickening. Its relationship to endothelial cell death and replacement. J Cell Biol. 1970 Oct;47(1):281–285. doi: 10.1083/jcb.47.1.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Williamson J. R., Kilo C. Basement-membrane thickening and diabetic microangiopathy. Diabetes. 1976;25(2 Suppl):925–927. [PubMed] [Google Scholar]
  34. Williamson J. R., Kilo C. Current status of capillary basement-membrane disease in diabetes mellitus. Diabetes. 1977 Jan;26(1):65–73. doi: 10.2337/diab.26.1.65. [DOI] [PubMed] [Google Scholar]
  35. Winegrad A. I., Greene D. A. The complications of diabetes mellitus. N Engl J Med. 1978 Jun 1;298(22):1250–1252. doi: 10.1056/NEJM197806012982208. [DOI] [PubMed] [Google Scholar]
  36. Wolinsky H. Effects of hypertension and its reversal on the thoracic aorta of male and female rats. Morphological and chemical studies. Circ Res. 1971 Jun;28(6):622–637. doi: 10.1161/01.res.28.6.622. [DOI] [PubMed] [Google Scholar]
  37. Wolinsky H., Goldfischer S., Capron L., Capron F., Coltoff-Schiller B., Kasak L. Hydrolase activities in the rat aorta. I. Effects of diabetes mellitus and insulin treatment. Circ Res. 1978 Jun;42(6):821–831. doi: 10.1161/01.res.42.6.821. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES