Acetylated polyamines in lungs from rats with monocrotaline-induced pneumotoxicity

Multiple lines of evidence implicate the polyamines, putrescine, spermidine, and spermine in the lung injury and hypertensive pulmonary vascular disease produced in rats by the pyrrolizidine alkaloid monocrotaline. While increases in lung polyamine content evoked by monocrotaline can be attributed in part to induction of the two rate-limiting enzymes in de novo polyamine synthesis, ornithine decarboxylase and S-adenosylmethionine decarboxylase, little attention has been paid to the role that catabolic interconversion processes might play in lung polyamine accumulation. Accordingly, the present study evaluated dose (10-60 mg/kg)- and time (0-21 days)-dependent effects of monocrotaline on lung contents of acetylated polyamines and on the activity of spermidine/spermine acetyltransferase (SAT), the enzyme affecting spermidine acetylation. A single subcutaneous injection of monocrotaline produced dose- and time-dependent increases in the lung content of N1-acetylspermidine. Neither N1-acetylspermine nor N1-acetylputrescine could be detected in lungs from control rats or from rats treated with monocrotaline. SAT activity also was increased in monocrotaline-treated rat lungs in a dose- and time-dependent manner that was closely related to increases in the lung burden of N1-acetylspermidine. As expected, monocrotaline also caused dose- and time-dependent elevations in the lung contents of the primary polyamines, putrescine, spermidine, and spermine. Right ventricular hypertrophy, an index of sustained pulmonary hypertension, did not develop in animals treated with 10 or 20 mg/kg monocrotaline despite elevations in the lung contents of putrescine and N1-acetylspermidine and increases in the activity of SAT. In contrast, 30 and 60 mg/kg monocrotaline provoked right ventricular hypertrophy accompanied by elevations in the primary polyamines, N1-acetyl spermidine and SAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)