Abstract:
:Previous work from this laboratory (J. S. Lazo, J. D. Catravas, and C. N. Gillis, Biochem. Pharmacol. 30, 2577-2584, 1981; J. D. Catraveras, J. S. Lazo, and C. N. Gillis, J. Pharmacol. Exp. Ther. 217, 524-529, 1981) demonstrated that subacute bleomycin (BLM) administration (5 mg/kg) to rabbits three times weekly for 4 weeks produced a marked decrease in serum angiotensin converting enzyme (ACE) activity in addition to producing both morphological and biochemical evidence of pulmonary endothelial damage. In this work, the reversibility of the decreased serum ACE activity and the biochemical and morphological status of the pulmonary endothelium after a substantial drug-free period in rabbits was examined. Rabbits were injected sc three times weekly for 4 weeks with vehicle or BLM (5 mg/kg) and then maintained drug free for an additional 6 or 7 weeks. Serum ACE activity decreased over 60% during the BLM treatment but did not return to control levels at any time during the drug-free period. The pulmonary endothelium, however, appeared undamaged. No decrease in pulmonary ACE activity was detected either in vitro or in vivo nor was the single-pass pulmonary removal in vivo of [3H]norepinephrine and 5-[14C]hydroxytryptamine different between BLM-treated and control rabbits after the drug-free period. In addition, no evidence of pulmonary endothelial damage was observed by light and electron microscopy. Thus, reduction in serum ACE activity appears to be a durable reflection of BLM toxicity in rabbits that persists even in the absence of any detectable biochemical or morphologic endothelial injury.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Lazo JS,Catravas JD,Dobuler KJ,Gillis CNdoi
10.1016/0041-008x(83)90309-5subject
Has Abstractpub_date
1983-06-30 00:00:00pages
276-82issue
2eissn
0041-008Xissn
1096-0333pii
0041-008X(83)90309-5journal_volume
69pub_type
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