Angiotensin-II activates apoptosis, proliferation and protein synthesis in the left heart ventricle of newborn albino rats.

Angiotensin II (ANG-II) is a critical regulator of various signaling pathways involved in growth and remodeling of the vascular, cardiac, and renal cells and tissues. Although it contributes to several physiologic and pathologic events in the cardiovascular system, its role in growth and differentiation of the newborn heart is still unclear. We analyzed the effect of ANG-II treatment on apoptosis, DNA synthesis, and nucleolar organizer regions (AgNORs) activity in newborn rat myocardium. Injections of ANG-II for 5-days caused significant increase of the 3H-thymidine labeling index (M+/-m) in the myocardium of 7-day-old rats (from 6.95+/-0.32% to 8.53+/-0.22%, p<0.05). There was also significant increase in the cross sectional surface area of cardiomyocytes (from 686+/-57 to 872+/-54 microm2, p<0.05), number of nucleoli (from 2.5+/-0.05 to 2.8+/-0.1, p<0.05), and nucleolar surface area (from 2.6+/-0.09 to 3.2+/-0.22 microm2, p<0.05). These changes were accompanied by significant increase in the apoptotic indices analyzed by TDT-mediated dUTP-biotin nick end-labeling (TUNEL) (from 0.044+/-0.01% to 0.093+/-0.01%, p<0.05). Interestingly, we found no differences in cell proliferation between the test and control animals after 21-45 days of age, which were injected with ANG-II in the first postnatal week. However, the area of cardiomyocytes and the number of nucleoli in 21-day-old rats continued to increase significantly. Our results indicate that ANG-II modulates cardiac growth during the neonatal period via stimulation of apoptosis, cell cycle events and cellular growth of cardiomyocytes and that these effects can persist up to 15 days after injection of ANG-II has been completed.