Myocardial cell growth and blood pressure development in neonatal spontaneously hypertensive rats.
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We evaluated the changing morphologic features of cardiac muscle cells (myocytes) and nuclei from neonatal spontaneously hypertensive rats (SHR) and their parent, normotensive strain Wistar Kyoto rats (WKY) and compared these with increasing heart weight and blood pressure development to determine if alterations in cell growth were present at this early stage of development. Femoral artery blood pressures were obtained from rats at 2 to 5-day intervals from birth to 21 days of age by using a micropipette servo-null pressure recording system. Tritiated thymidine autoradiography was used to study myocyte nuclear development, and isolated myocytes were prepared to evaluate cell-size changes by using a Coulter Counter system (Coulter Electronics, Hialeah, Florida). Heart weight and blood pressure were elevated in SHR when compared to WKY at birth. Myocytes were all mononucleated at birth in both strains and were of equal size, demonstrating that the larger heart mass in SHR was due to an increased number of cells. Heart weight relative to body weight remained greater in SHR when compared to WKY throughout the 28-day study period, but cell numbers became equal in the two strains by the 2nd week. A this time (6 to 9 days postpartum) blood pressure was also similar in both strains, but increased significantly again in SHR by 15 and 21 days of age. Cell maturation occurred earlier in SHR than in WKY as indicated by an earlier development of binucleate myocytes and there was an earlier initiation of hypertrophic myocyte growth in SHR. Increase in SHR cell size occurred at a time when blood pressures were not different, suggesting that greater cell size in SHR than in WKY was not due to differences in blood pressure. Therefore, when compared to the WKY, the SHR had three phases of altered cell growth: a first phase of accelerated hyperplastic growth during the fetal period, and a second phase (6 to 12 days of age) of earlier initiation of hypertrophic cell growth and increased myocyte size. The SHR myocyte changes in the second phase occurred while the SHR and the WKY blood pressures were not significantly different. Finally, in a third phase (at 15 days of age and over), SHR had a sustained increase in myocyte size as well as elevated blood pressure.
