ANGIOTENSIN-II MEDIATED GROWTH AND ANTIGROWTH EFFECTS IN CULTURED NEONATAL RAT CARDIAC MYOCYTES AND FIBROBLASTS

Angiotensin II (Ang II) stimulates cardiovascular growth and remodelin g via AT(1) receptors. Recent experiments have shown that Ang II may a lso exert antiproliferative effects via AT(2) receptors. We studied th e effects of Ang II on protein and DNA content and synthesis rate in u nstimulated and endothelin-1 (ET-1)-stimulated neonatal rat cardiomyoc ytes and fibroblasts. isolated from 1-3-day-old Wistar strain pups. To tal protein and rotal DNA, as well as [H-3]leucine and [H-3]thymidine incorporation were measured following incubation with either vehicle, Ang II, ET-1 or Ang II+ET-1, both in the presence or absence of the AT (1) receptor blocker losartan or the AT(2) receptor blocker PD123319. In myocytes, ET-1 increased total protein (+38% relative to control) a s well as [H-3]leucine (+66%) and [H-3]thymidine (+77%) incorporation. Ang II did not affect any of these parameters, nor did it influence t he ET-1-induced responses. However, in the presence of PD123319 Ang II stimulated [H-3]leucine (+24%) and [H-3]thymidine (+30%) incorporatio n. In fibroblasts, ET-1 and Ang II did not significantly affect total DNA and [H-3]thymidine incorporation. Ang II tended to increase total protein in these cells, an effect which was significant only in the pr esence of PD123319 (+17%). Ang II stimulated [H-3]leucine incorporatio n (+24%) in fibroblasts. This effect was absent with losartan and enha nced in the presence of PD123319. These data demonstrate that AT(1) re ceptor-mediated proliferative effects of Ang II in neonatal cardiac ce lls may become apparent only when its AT(2) receptor-mediated antigrow th effects are blocked. The net growth effect of Ang II therefore depe nds on the cellular AT(1)/AT(2) receptor ratio. Ang II does not appear to interfere with ET-1-induced effects. (C) 1997 Academic Press Limit ed.