Early Proliferative Changes in Hearts of Hypertensive Goldblatt Rats: an Immunohistochemical and Flow-cytometrical Study
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Hyperplasia of myocytes in cardiac adaptation is a rare event in the mammalian cardiac muscle. Recent findings support the concept that proliferation of myocytes in the adult mammalian heart may be induced after a prolonged increase in pressure load on the myocardium. To determine whether short-term hypertension leads to hyperplasia of myocyte nuclei in the rat heart renal hypertension was produced in 12 Wistar rats. As soon as hypertension occurred, bromodeoxyuridine (BrdU) (50 mg/kg/day) was injected intraperitoneally on three subsequent days. Twelve sham-operated rats served as controls. After 3 days, the left cardiac ventricle was excised and double-staining with anti-BrdU antibody and propidium iodide was performed to determine the phase of cell-cycle of the BrdU-positive cells by flow-cytometry. Immunohistochemical double-staining with desmin, smooth muscle actin, vimentin, and BrdU was done to classify the BrdU-positive cells. Most of the BrdU-positive cells were in the G0/G1-phase of the cell-cycle, suggesting cell proliferation or DNA-repair have taken place; polyploidy was not observed. In the hypertensive group (4.62% +/- 2.36) significantly more cells incorporated BrdU than in the control group (1.46% +/- 0.96). Immunohistochemically, the majority of the BrdU-positive cells consisted of fibrocytes, smooth muscle cells, and endothelial cells. Only 0.35% +/- 0.26 of cardiac myocytes in the normotensive group showed positive BrdU-staining compared to 0.48% +/- 0.32 in the hypertensive group. This difference was statistically not significant. This study showed that early after onset of hypertension proliferation of non-myocytes, but not of myocytes occurred. DNA synthesis is limited almost completely to the interstitial cells and does not occur in any significant extent in cardiac myocytes. In conclusion, hyperplasia of cardiac myocytes is not observed at early stages of hypertension, but it may develop at a late stage of cardiac adaptation.