Surfactant disposition in rats with monocrotaline-induced pneumotoxicity.
Monocrotaline (MCT)-treated rats exhibit airways and gas exchange abnormalities which precede development of sustained pulmonary hypertension (Lai et al., 1991). Because the density of type II pneumocytes is reduced in MCT-treated rat lungs (Wilson and Segall, 1990), decreased abundance or activity of type II pneumocyte-derived surfactant may contribute 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 activity. As an initial means of discriminating between these possibilities, the amount, surface activity, and synthesis rate of surfactant was examined in rats at 1, 2, and 3 weeks after MCT administration. The amounts of surfactant phospholipid and protein recovered in bronchoalveolar lavage fluid did not differ substantially between control and MCT-treated rats at any time post MCT administration. Similarly, neither the 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 in lung explants, as determined by incorporation of [3H]glycerol into phospholipid, also was not different between MCT-treated and control rats at any time after MCT administration. MCT treatment failed to alter the distribution of [3H]glycerol into surfactant phospholipid. Collectively, these data indicate that airways abnormalities in MCT-treated rats cannot be ascribed to a reduction in the abundance or the activity of surfactant. Furthermore, in light of previous studies indicating that the density of type II pneumocytes is reduced in MCT pneumotoxicity, the present findings suggest that surfactant regulatory pathways must undergo a compensatory response that preserves normal functional status.
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky A.B. Chandler Medical Center, Lexington 40536-0082.
P M
PM
Bummer
J A
JA
Baughn
L P
LP
Sanders
K R
KR
Absher
W N
WN
O'Connor
J W
JW
Olson
M N
MN
Gillespie
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005990:Glycerol / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013500:Surface Tension / Q000187:drug effects
D010743:Phospholipids; D011663:Pulmonary Surfactants; D016686:Monocrotaline; D005990:Glycerol