PRENATAL TREATMENT WITH CAPTOPRIL INDUCES EMPHYSEMA IN RAT LUNG DEVELOPMENT

CAPELARI, DN; SANCHEZ SI; FUENTES LB; ORTEGA HH; CIUFFO GM

San Juan

Congreso; Reunion Anual Soc. de Biologia de Cuyo; 2011

Soc. de Biologia de Cuyo

Angiotensin-converting enzyme inhibitors (ACEI) have been widely used in hypertension treatment. However, the use of ACEI during pregnancy is contraindicated for risks of fetopathy. We investigated the effect of captopril prenatal treatment in lung development. Wistar rats were treated with captopril (2,85 mg/kg/day) delivered subcutaneously with osmotic mini-pumps during the last week of pregnancy. Pup‘s lungs at four different postnatal ages (P0, P8, P15 and P30) were evaluated by morphological, histomorphometric and immunohistochemistry staining analysis. Captopril treatment significantly decreased body and lung weights at P0 and P8. Histological study evidenced a substantial destruction of alveolar walls in treated rats, resulting in enlargement of distal airway spaces at P8, P15 and P30, demonstrated by significant increase in the interalveolar wall distance, quantified by mean linear intercept (MLI). Cellular proliferation was evaluated using PCNA (proliferating cell nuclear antigen). The percentage of PCNA-positively stained alveolar epithelial cells in the treated group was significantly higher at P15 and P30, respect to the control group. Cell proliferation decreased with age in control animals. However, in captopriltreated lungs the relative number of PCNA immunopositive nuclei remains high during the studied ages. These findings support the hypothesis of a functional renin-angiotensin-system required for normal lung development.