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Effects of combined renovascular hypertension and diabetes mellitus on myocardial cells, non-vascular interstitium and capillaries: a stereological study on rat hearts

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Summary

The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive non-diabetic animals were compared to diabetic and non-diabetic controls. Hypertension was established for 12 weeks by a surgical stenosis of the left renal artery; diabetes mellitus was maintained for 8 weeks by a single intraperitoneal injection of 60 mg/kg streptozotocin. Light microscopic stereology did not reveal significant divergences between diabetic hypertensives and non-diabetic hypertensives. Hypertension induced a focal perivascular and interstitial fibrosis with increased volume densities of non-vascular interstitium and fibrosis (P<0.001). Capillary density (QA) was decreased in transverse sections (P<0.01) and increased in longitudinal sections (P<0.01). This indicates a three-dimensional remodelling of the capillary bed with an increased number of obliquely running capillaries. At least the length density (LV) of capillaries (mm/mm3) tends to be normalized in long-term renovascular hypertension. At the ultrastructural level, a synergism of hypertension and diabetes mellitus was observed: the volume ratio of mitochondria to myofibrils was significantly decreased in hypertensive diabetics, but not in non-diabetic hypertensives or in diabetics. This may enhance the risk of cardiac deterioration. We conclude that the primary target of the synergistic damage in hypertensive diabetic heart muscle disease is the myocardial cell and not the cardiac interstitium.

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References

  • Anversa P, Olivetti G, Melissari M, Loud AV (1980) Stereological measurement of cellular and subcellular hypertrophy and hyperplasia in the papillary muscle of adult rat. J Mol Cell Cardiol 12:781–795

    Google Scholar 

  • Baandrup U, Ledet T, Rasch R (1981) Experimental diabetic cardiopathy preventable by insulin treatment. Lab Invest 45:169–173

    Google Scholar 

  • Bhimji S, Godin DV, McNeill JH (1986) Insulin reversal of biochemical changes in hearts from diabetic rats. Am J Physiol 251:H 670–675

    Google Scholar 

  • Breisch EA, Houser SR, Carey RA, Spann JF, Bove AA (1980) Myocardial blood flow and capillary density in chronic pressure overload of the feline left ventricle. Cardiovas Res 14:469–475

    Google Scholar 

  • Breisch EA, White C, Bloor CM (1984) Myocardial characteristics of pressure overload hypertrophy. Lab Invest 51:333–341

    Google Scholar 

  • Dillmann WH (1980) Diabetes mellitus induces changes in cardiac myosin of the rat. Diabetes 29:579–582

    Google Scholar 

  • Di Sant'Agnese PA, De Mesy Jensen KL (1984) Dibasic staining of large epoxy sections and applications to surgical pathology. Am J Clin Pathol 80:25–29

    Google Scholar 

  • Factor SM, Minase T, Sonnenblick EH (1980) Clinical and morphological features of human hypertensive-diabetic cardiomyopathy. Am Heart J 99:446–458

    Google Scholar 

  • Factor SM, Minase T, Bhan R, Wolinski H, Sonnenblick EH (1981) Hypertensive-diabetic cardiomyopathy in the rat. An experimental model of human disease. Am J Pathol 102:219–317

    Google Scholar 

  • Fein FS, Capasso JM, Aronson RS, Cho S, Nordin C, Miller-Green B, Sonnenblick EH, Factor SM (1984) Combined renovascular hypertension and diabetes in rats: a new preparation of congestive cardiomyopathy. Circulation 70:318–330

    Google Scholar 

  • Fein FS, Cho S, Zola BE, Miller B, Factor SM (1989) Biventricular damage with right ventricular predominance. Am J Pathol 134:1159–1166

    Google Scholar 

  • Frenzel H, Buerrig KF, Kasper M, Schwartzkopff B, Roesen P (1985) Funktionelle und morphometrische Untersuchungen an Kapillaren und Herzmuskelzellen im Herzen diabetischer Ratten. Verh Dtsch Ges Path 69:657

    Google Scholar 

  • Hsiao YC, Suzuki KI, Abe H, Toyoda T (1987) Ultrastructural alterations in cardiac muscle of diabetic BB Wistar rats. Virchows Arch A 411:45–52

    Google Scholar 

  • Jackson CV, McGrath GM, Tahiliani AG, Vadlamudi RVSV, McNeill JH (1985) A functional and ultrastructural analysis of experimental diabetic rat myocardium. Diabetes 34:873–876

    Google Scholar 

  • Jacob R (1983) Chronic reactions of myocardium at the myofibrillar level. Reflections on “adaption” and “disease” based on the biology of long-term cardiac overload. In: Jacob R, GĂĽlch RW, Kissling G (eds) Cardiac adaptation to hemodynamic overload, training and stress. Steinkopff, Darmstadt: pp 89–106

    Google Scholar 

  • Jalil JE, Doering CW, Janicki JS, Pick R, Shroff SG, Weber KT (1989) Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle. Circ Res 64:1041–1050

    Google Scholar 

  • Kannel WB, Hjortland M, Castelli WP (1974) Role of diabetes in congestive heart failure: the Framingham Study. Am J Cardiol 34:29–34

    Google Scholar 

  • Mall G, Reinhard H, Kayser K, Rossner JA (1978) An effective morphometric method for electron microscopic studies on papillary muscles. Virchows Arch [A] 379:219–228

    Google Scholar 

  • Mall G, Mattfeldt T, Möbius HJ, Leonhard R (1986) Stereological study on the rat heart in chronic alimentary thiamine deficiency — absence of myocardial changes despite starvation. J Mol Gen Cardiol 18:635–643

    Google Scholar 

  • Mall G, Klingel K, Hasslacher GH, Mann J, Mattfeldt T, Baust H, Waldherr R (1987a) Synergistic effects of diabetes mellitus and renovascular hypertension on the rat heart — stereological investigations on papillary muscles. Virchows Arch [A] 411:531–542

    Google Scholar 

  • Mall G, Schikora I, Mattfeldt T, Bodle R (1987b) Dipyridamoleinduced neoformation of capillaries in the rat heart. Lab Invest 57:86–93

    Google Scholar 

  • Mall G, Rambausek M, Neumeister A, Kollmar S, Vetterlein F, Ritz E (1988) Myocardial interstitial fibrosis in experimental uraemia — implications for cardiac compliance. Kidney Int 33:804–811

    Google Scholar 

  • Mall G, Huther W, Schneider J, Lundin P, Ritz E (1990a) Diffuse intramyocardiocytic fibrosis in uraemic patients. Nephrol Dial Transplant 5:39–44

    Google Scholar 

  • Mall G, Zimmer G, Baden S, Mattfeldt T (1990b) Capillary neoformation in the rat heart — a stereological study on papillary muscles in hypertrophy and physiologic growth. Basic Res Cardiol 85:531–540

    Google Scholar 

  • Mall G (1991) Morphometric study on the rat heart in combined renovascular hypertension and diabetes mellitus. In: Nagano N, Dhalla NS (eds) The diabetic heart. Raven Press, New York, pp 115–124

    Google Scholar 

  • Mattfeldt T, Mall G (1984) Estimation of length and surface of anisotropic capillaries. J Microsc 135:181–190

    Google Scholar 

  • McKee PA, Castelli WP, McNamara PM, Kannel WB (1971) The natural history of congestive heart failure: the Framingham study. N Engl J Med 285:1441–1446

    Google Scholar 

  • Möhring J, Petri M, Szokol M, Haack D, Möhring B (1976) Effects of saline drinking on malignant course of renal hypertension in rats. Am J Physiol 230:849–857

    Google Scholar 

  • Pierce GN, Dhalla NS (1981) Cardiac myofibrillar ATPase activity in diabetic rats. J Mol Cell Cardiol 13:1063–1069

    Google Scholar 

  • Rodrigues G, McNeill JH (1986) Cardiac function in spontaneously hypertensive diabetic rats. Am J Physiol 521:H571-H586

    Google Scholar 

  • Sachs L (1974) Angewandte Statistik. Springer-Verlag Berlin Heidelberg New York, p 386

    Google Scholar 

  • Thiedemann KU, Holubarsch C, Medugorac I, Jacob R (1983) Connective tissue content and myocardial stiffness in pressure overload hypertrophy. A combined study of morphologic, morphometric, biochemical, and mechanical parameters. Basic Res Cardiol 78:140–155

    Google Scholar 

  • Weber KT, Janicki JS, Pick R, Abrahams C, Shroff SG, Bashey RI, Chen RM (1987) Collagen in the hypertrophied, pressureoverloaded myocardium. Circulation 75 [Suppl I]:1–40

    Google Scholar 

  • Weibel ER (1979) Stereological methods, vol 1. Academic Press, London, pp 26–36

    Google Scholar 

  • Wollenberger A, Schulze W (1962) Ăśber das Volumenverhältnis von Mitochondrien zu Myofibrillen im chronisch ĂĽberlasteten, hypertrophierten Herzen. Naturwissenschaften 49:161–162

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Heidelberg, W-6900, Heidelberg, Germany

    Marc Fischer, Gabriele Wiest, Ismail Tekesin, Kerstin Amann, Harald Derks & Gerhard Mall

  2. Department of Internal Medicine, University of Heidelberg, W-6900, Heidelberg, Germany

    Johannes Mann & Christian Hasslacher

Authors
  1. Marc Fischer
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  2. Gabriele Wiest
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  3. Ismail Tekesin
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  4. Kerstin Amann
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  5. Johannes Mann
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  6. Christian Hasslacher
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  7. Harald Derks
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  8. Gerhard Mall
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Additional information

Dedicated to Prof. Dr. med. G. Seifert on the occasion of his 70th birthday

Preliminary results of this study have been published in: Mall G (1991) Morphometric study on the rat heart in combined renovascular hypertension and diabetes mellitus. In: Nagano N, Dhalla NS (eds) The diabetic heart. Raven Press, New York, pp 115–124

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Fischer, M., Wiest, G., Tekesin, I. et al. Effects of combined renovascular hypertension and diabetes mellitus on myocardial cells, non-vascular interstitium and capillaries: a stereological study on rat hearts. Vichows Archiv A Pathol Anat 420, 499–506 (1992). https://doi.org/10.1007/BF01600254

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  • DOI: https://doi.org/10.1007/BF01600254

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