Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Apr;85(4):994–997. doi: 10.1172/JCI114576

Hypertensive cardiomyopathy. Myocyte nuclei hyperplasia in the mammalian rat heart.

P Anversa 1, T Palackal 1, E H Sonnenblick 1, G Olivetti 1, J M Capasso 1
PMCID: PMC296527  PMID: 2138635

Abstract

To determine whether long-term hypertension leads to hyperplasia of myocyte nuclei in the heart, a phenomenon suspected to occur in humans, renal hypertension was produced in rats and the animals were killed 8 mo later. Arterial blood pressure remained elevated for approximately 5 mo, but decreased progressively in the last 3 mo so that at 8 mo this parameter was practically identical to that found in controls. Moreover, left ventricular end diastolic pressure was markedly increased in experimental animals in association with a substantial decrease in left ventricular dP/dt. The alteration of these physiological measurements was indicative of severe ventricular dysfunction. Quantitative analysis of the transmural distribution of myocyte nuclei in the left ventricle showed 36 and 23% increases in myocyte nuclei concentration in the epimyocardium and endomyocardium, respectively. These changes in nuclei were accompanied by 25 and 16% reductions in myocyte cell volume per nucleus in the outer and inner layers of the wall. In conclusion, long-term hypertension leads to impairment of ventricular function and proliferation of nuclei in myocytes.

Full text

PDF
995

Images in this article

Selected References

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

  1. Anversa P., Beghi C., Kikkawa Y., Olivetti G. Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth. Circ Res. 1986 Jan;58(1):26–37. doi: 10.1161/01.res.58.1.26. [DOI] [PubMed] [Google Scholar]
  2. Anversa P., Beghi C., Levicky V., McDonald S. L., Kikkawa Y. Morphometry of right ventricular hypertrophy induced by strenuous exercise in rat. Am J Physiol. 1982 Dec;243(6):H856–H861. doi: 10.1152/ajpheart.1982.243.6.H856. [DOI] [PubMed] [Google Scholar]
  3. Anversa P., Olivetti G., Loud A. V. Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes. Circ Res. 1980 Apr;46(4):495–502. doi: 10.1161/01.res.46.4.495. [DOI] [PubMed] [Google Scholar]
  4. Astorri E., Bolognesi R., Colla B., Chizzola A., Visioli O. Left ventricular hypertrophy: a cytometric study on 42 human hearts. J Mol Cell Cardiol. 1977 Sep;9(9):763–775. doi: 10.1016/s0022-2828(77)80021-7. [DOI] [PubMed] [Google Scholar]
  5. Astorri E., Chizzola A., Visioli O., Anversa P., Olivetti G., Vitali-Mazza L. Right ventricular hypertrophy--a cytometric study on 55 human hearts. J Mol Cell Cardiol. 1971 Jun;2(2):99–110. doi: 10.1016/0022-2828(71)90064-2. [DOI] [PubMed] [Google Scholar]
  6. Bishop S. P., Oparil S., Reynolds R. H., Drummond J. L. Regional myocyte size in normotensive and spontaneously hypertensive rats. Hypertension. 1979 Jul-Aug;1(4):378–383. doi: 10.1161/01.hyp.1.4.378. [DOI] [PubMed] [Google Scholar]
  7. Capasso J. M., Malhotra A., Scheuer J., Sonnenblick E. H. Myocardial biochemical, contractile, and electrical performance after imposition of hypertension in young and old rats. Circ Res. 1986 Apr;58(4):445–460. doi: 10.1161/01.res.58.4.445. [DOI] [PubMed] [Google Scholar]
  8. Capasso J. M., Strobeck J. E., Malhotra A., Scheuer J., Sonnenblick E. H. Contractile behavior of rat myocardium after reversal of hypertensive hypertrophy. Am J Physiol. 1982 May;242(5):H882–H889. doi: 10.1152/ajpheart.1982.242.5.H882. [DOI] [PubMed] [Google Scholar]
  9. Capasso J. M., Strobeck J. E., Sonnenblick E. H. Myocardial mechanical alterations during gradual onset long-term hypertension in rats. Am J Physiol. 1981 Sep;241(3):H435–H441. doi: 10.1152/ajpheart.1981.241.3.H435. [DOI] [PubMed] [Google Scholar]
  10. Claycomb W. C. Biochemical aspects of cardiac muscle differentiation. Deoxyribonucleic acid synthesis and nuclear and cytoplasmic deoxyribonucleic acid polymerase activity. J Biol Chem. 1975 May 10;250(9):3229–3235. [PubMed] [Google Scholar]
  11. Claycomb W. C. Cardiac-muscle hypertrophy. Differentiation and growth of the heart cell during development. Biochem J. 1977 Dec 15;168(3):599–601. doi: 10.1042/bj1680599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Claycomb W. C., Moses R. L. Culture of atrial and ventricular cardiac muscle cells from the adult squirrel monkey Saimiri sciureus. Exp Cell Res. 1985 Nov;161(1):95–100. doi: 10.1016/0014-4827(85)90493-8. [DOI] [PubMed] [Google Scholar]
  13. Claycomb W. C., Moses R. L. Growth factors and TPA stimulate DNA synthesis and alter the morphology of cultured terminally differentiated adult rat cardiac muscle cells. Dev Biol. 1988 Jun;127(2):257–265. doi: 10.1016/0012-1606(88)90313-2. [DOI] [PubMed] [Google Scholar]
  14. Engelmann G. L., Vitullo J. C., Gerrity R. G. Age-related changes in ploidy levels and biochemical parameters in cardiac myocytes isolated from spontaneously hypertensive rats. Circ Res. 1986 Jan;58(1):137–147. doi: 10.1161/01.res.58.1.137. [DOI] [PubMed] [Google Scholar]
  15. Fraticelli A., Josephson R., Danziger R., Lakatta E., Spurgeon H. Morphological and contractile characteristics of rat cardiac myocytes from maturation to senescence. Am J Physiol. 1989 Jul;257(1 Pt 2):H259–H265. doi: 10.1152/ajpheart.1989.257.1.H259. [DOI] [PubMed] [Google Scholar]
  16. Grove D., Zak R., Nair K. G., Aschenbrenner V. Biochemical correlates of cardiac hypertrophy. IV. Observations on the cellular organization of growth during myocardial hypertrophy in the rat. Circ Res. 1969 Oct;25(4):473–485. doi: 10.1161/01.res.25.4.473. [DOI] [PubMed] [Google Scholar]
  17. Katzberg A. A., Farmer B. B., Harris R. A. The predominance of binucleation in isolated rat heart myocytes. Am J Anat. 1977 Aug;149(4):489–499. doi: 10.1002/aja.1001490406. [DOI] [PubMed] [Google Scholar]
  18. LINZBACH A. J. Heart failure from the point of view of quantitative anatomy. Am J Cardiol. 1960 Mar;5:370–382. doi: 10.1016/0002-9149(60)90084-9. [DOI] [PubMed] [Google Scholar]
  19. MAURO A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961 Feb;9:493–495. doi: 10.1083/jcb.9.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Oberpriller J. O., Ferrans V. J., Carroll R. J. Changes in DNA content, number of nuclei and cellular dimensions of young rat atrial myocytes in response to left coronary artery ligation. J Mol Cell Cardiol. 1983 Jan;15(1):31–42. doi: 10.1016/0022-2828(83)90305-x. [DOI] [PubMed] [Google Scholar]
  21. Olivetti G., Ricci R., Anversa P. Hyperplasia of myocyte nuclei in long-term cardiac hypertrophy in rats. J Clin Invest. 1987 Dec;80(6):1818–1821. doi: 10.1172/JCI113278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Olivetti G., Ricci R., Lagrasta C., Maniga E., Sonnenblick E. H., Anversa P. Cellular basis of wall remodeling in long-term pressure overload-induced right ventricular hypertrophy in rats. Circ Res. 1988 Sep;63(3):648–657. doi: 10.1161/01.res.63.3.648. [DOI] [PubMed] [Google Scholar]
  23. Rumyantsev P. P., Kassem A. M. Cumulative indices of DNA synthesizing myocytes in different compartments of the working myocardium and conductive system of the rat's heart muscle following extensive left ventricle infarction. Virchows Arch B Cell Pathol. 1976 May 26;20(4):329–342. doi: 10.1007/BF02890352. [DOI] [PubMed] [Google Scholar]
  24. Schwartz S. M., Campbell G. R., Campbell J. H. Replication of smooth muscle cells in vascular disease. Circ Res. 1986 Apr;58(4):427–444. doi: 10.1161/01.res.58.4.427. [DOI] [PubMed] [Google Scholar]
  25. Sorenson A. L., Tepper D., Sonnenblick E. H., Robinson T. F., Capasso J. M. Size and shape of enzymatically isolated ventricular myocytes from rats and cardiomyopathic hamsters. Cardiovasc Res. 1985 Dec;19(12):793–799. doi: 10.1093/cvr/19.12.793. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES