Prolonged activation of rat lung ornithine decarboxylase in monocrotaline-induced pulmonary hypertension

Abstract

Polyamines are believed to have an essential role in cellular growth and differentiation. Activation of ornithine decarboxylase, the initial rate-limiting enzyme in polyamine biosynthesis, is an early event characteristic of cell growth processes. Monocrotaline-induced pneumotoxicity is associated with cellular hypertrophy and proliferation, most notably pronounced medial thickening of pulmonary arterioles and hypertrophy of right ventricular myocardial cells. We reasoned that polyamines may be causally related to these events and, therefore, elevations in lung and right ventricular ornithine decarboxylase activities might precede development of pulmonary hypertension and right ventricular hypertrophy. To test this hypothesis adult male rats were given monocrotaline (105 mg/kg, s.c.); lung and right and left ventricular ornithine decarboxylase activities, pulmonary artery pressure, and right ventricular hypertrophy were assessed at 1, 4, 7, 10, 14, 16 and 21 days post treatment. Lung ornithine decarboxylase activity was increased approximately 8-fold on day 1 and remained elevated through day 7. Right ventricular ornithine decarboxylase activity was not elevated above control values at any time. Elevated pulmonary artery pressure and right ventricular hypertrophy were not apparent until day 16 and day 14 respectively. Thus, sustained activation of lung ornithine decarboxylase occurred at least 1 week prior to the development of pulmonary hypertension, suggesting that polyamines may play an important role in the pulmonary vascular remodeling that accompanies monocrotaline-induced pneumotoxicity.