Multiple lines of evidence suggest that the polyamines, a family of Iow-molecular-welght organic cations with documented regulatory roles In cell growth and differentiation, are Involved with hyperplastic and hypertrophic responses of lung cells underlying hypertensive pulmonary vascular disease. Little is known, however, of the factor (s) Initiating polyamine synthesis in pulmonary hypertension. This study tested the key aspects of the hypothesis that augmented polyamine synthesis, and attendent vascular structural alterations in monocrotallne (MCT)-treated rats can be ascribed to elaboration of an epidermal growth factor (EGF)-lIke mitogen. In lungs of rats treated

4 days previously with 60 mg/kg MCT, EGF-llke Immunoreactivity was detected diffusely throughout perivascular regions. Intravenous administration of human recombinant EGF (125pg/h) to rats for

1 wk was associated with medial thickening In pulmonary arteries between 100 and 200 11m in diameter, significant Increases in lung polyamine contents, and a moderate elevation in mean pulmonary arterial pressure. These observations Indicate that EGFcan be detected in the lungs of MCT-treated rats and that exogenous EGF mimics some of the actions of MCTon the rat lung. It Is thus reasonable to speculate that an EGF-llke mitogen may participate in the response to MCT in part through a polyamine-dependent mechanism. AM REV RESPIR DIS 1989; 140: 1463-1466