Biochemical characterization of neonatal cardiomyocyte development in normotensive and hypertensive rats.
Final cellular replication and functional maturation of the mammalian ventricular myocyte (cardiomyocyte) is known to occur during the first 2 post-natal weeks in rodents, yet the exact temporal sequence of events remains to be clearly established. When a genetic predisposition toward ventricular hypertrophy also manifests its influence during this time period, possible growth aberrations may occur. Using the spontaneously hypertensive rat (SHR) as an animal model, we have determined that biochemical and morphological indices of cardiomyocyte replicative deficits occur during the first 5 to 8 post-natal days relative to the normotensive control strain, Wistar Kyoto (WKY). Reduced ventricular nucleic acid (DNA and RNA) content and disproportionate RNA- and protein-DNA ratios were found in the neonatal SHR. Incorporation of tritiated thymidine into acid precipitable DNA during the first 5 postnatal days was also reduced in the SHR. Morphological evidence of reduced thymidine incorporation was determined autoradiographically at the cellular and nuclear level using isolated cells and nuclei, respectively. The results of our study indicate that SHR cardiomyocyte hyperplasia is reduced during the first 5 to 8 post-natal days when the last "window" of ventricular myocyte cellular replication occurs. Therefore, the maturing ventricle of the neonatal SHR contains fewer cardiomyocytes than its normotensive control and these cells appear to enter a hypertrophic growth phase at an accelerated rate.
Engelmann
G L
GL
Research Institute of the Cleveland Clinic Foundation, Department of Heart and Hypertension, OH 44106.
Gerrity
R G
RG
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D012313:RNA; D004247:DNA; D013936:Thymidine