EFFECT OF PRENATAL ACE INHIBITION ON MEDIATORS OF APOPTOTIC SIGNALLING DURING POSTNATAL LUNG DEVELOPMENT

CAPELARI D. N.; FUENTES L. B; CIUFFO G. M

Rosario

Congreso; Soc. de Farmacologia Experimental; 2009

Soc. Farmacología Experimental

Apoptosis or programmed cell death is an important component of different processes including normal cell turnover, proper development and chemical-induced cell death.  Apoptosis is a process characterized by a set of morphologic changes and energy-dependent biochemical mechanisms. Bcl-2 family members determine cell death and survival by controlling mitochondrial membrane ion permeability, cytochrome c release, and the subsequent activation of caspase. The aim of this study was to investigate the effect of prenatal ACE inhibition on mediators of apoptotic signalling in postnatal lung tissue development. Mini-osmotic pumps with enalapril or saline solution were implanted in pregnant Wistar rats during the last week of pregnancy. Pup`s lungs at four different ages: PND0, PND8, PND15 and PND30 were evaluated. The expression of anti-apoptotic Bcl2 or pro-apoptotic BAX gene was analysed by RT-PCR, and caspase-3 activity was confirmed by Western blot analysis. Semiquantitative assessment in both groups indicated similar result with significant up-regulation of Bcl2 expression (ANOVA, P<0.001) at PND8 and PND15 respect to PND0 and PND30. Moreover, we found high and constitutive BAX expression with no significant differences during development. Proteolysis of procaspase-3 was detected with high activation at PND0 and PND30. Hoechst staining demonstrated presence of apoptotic cells. In conclusion, the observations suggest that occurrence of apoptosis plays an important role in lung morphogenesis.