SURFACTANT DISPOSITION IN RATS WITH MONOCROTALINE-INDUCED PNEUMOTOXICITY

Monocrotaline (MCT)-treated rats exhibit airways and gas exchange abno rmalities which precede development of sustained pulmonary hypertensio n (Lai et al., 1991). Because the density of type II pneumocytes is re duced in MCT-treated rat lungs (Wilson and Segall, 1990), decreased ab undance or activity of type II pneumocyte-derived surfactant may contr ibute to pulmonary dysfunction. On the other hand, since the remaining type II pneumocytes undergo an apparent hypertrophic response, it is possible that they compensate for the reduction in population density by elaborating more surfactant or surfactant with enhanced surface act ivity. As an initial means of discriminating between these possibiliti es, the amount, surface activity, and synthesis rate of surfactant was examined in rats at 1,2, and 3 weeks after MCT administration. The am ounts of surfactant phospholipid and protein recovered in bronchoalveo lar lavage fluid did not differ substantially between control and MCT- treated rats at any time post MCT administration. Similarly, neither t he initial rate of surface tension reduction nor the maximum reduction in surface tension differed between surfactant preparations recovered from control and MCT-treated rats. The rate of surfactant synthesis i n lung explants, as determined by incorporation of [H-3]glycerol into phospholipid, also was not different between MCT-treated and control r ats at any time after MCT administration. MCT treatment failed to alte r the distribution of [H-3]glycerol into surfactant phospholipid. Coll ectively, these data indicate that airways abnormalities in MCT-treate d rats cannot be ascribed to a reduction in the abundance or the activ ity of surfactant. Furthermore, in light of previous studies indicatin g that the density of type II pneumocytes is reduced in MCT pneumotoxi city, the present findings suggest that surfactant regulatory pathways must undergo a compensatory response that preserves normal functional status.