Altered balance between cell replication and apoptosis in hearts and kidneys of newborn SHR

Apoptosis is involved in neonatal remodeling of organs of the cardiovascular system. Since we previously reported hyperplasia of these organs at birth in several forms of genetic hypertension, the aim of this study was to determine whether alterations of the apoptotic process could explain our findings. The heart, aorta, and kidneys of newborn Wistar-Kyoto and spontaneously hypertensive rats were harvested 24 hours after an injection of [3H]thymidine. DNA was extracted to measure its specific activity (index of DNA synthesis) and DNA fragmentation as an estimation of apoptosis. All organs studied showed an increased weight to body weight ratio in spontaneously hypertensive rats. Twenty-four hours after birth, DNA synthesis in all organs of spontaneously hypertensive rats was comparable to that in normotensive rats. However, apoptosis was markedly decreased in the heart and kidneys of newborn spontaneously hypertensive rats compared with their normotensive controls. In the aorta, apoptosis was reduced, but not significantly. Calculation of a proliferation index (DNA synthesis/fragmentation) revealed a significant increase of heart proliferation, with a similar trend in the aorta and kidneys. In addition, we found a negative correlation between heart weight and DNA fragmentation. Although other factors may influence hyperplasia of the aorta, we propose that a reduction of apoptotic activity is responsible, at least in part, for heart and kidney hyperplasia in newborn spontaneously hypertensive rats.