INCREASED TYPE-I PROCOLLAGEN MESSENGER-RNA IN AIRWAYS AND PULMONARY VESSELS AFTER VAGAL DENERVATION IN RATS

To test the hypothesis that increased airway strain resulting from lun g denervation initiates a fibroproliferative response in the airways, we compared the transcriptional expressions of alpha(1)(I)-procollagen and tropoelastin in the lungs of rats subjected to unilateral vagal d enervation, unilateral vagal denervation combined with ipsilateral phr enectomy, or thoracotomy without denervation (controls). We found incr eases in alpha(1)(I)-procollagen messenger ribonucleic acids (mRNAs) i n the submucosa of the airways and the adventitia of airways and pulmo nary vessels of the denervated lungs in 31% of the rats subjected to u nilateral denervation (with and without phrenectomy), and in none of t he controls. The increased transcripts were associated with collagen d eposition in the peribronchial and perivascular tissue, and occasional ly with cell proliferation leading to occlusion of the airway and vasc ular lumina. Unilateral phrenectomy did not decrease the frequency wit h which production of Type I procollagen was upregulated, suggesting t hat the upregulation was not entirely dependent on airway strain. Trop oelastin expression was not influenced by denervation. Our results ind icate that the autonomic nervous system has a previously unsuspected t rophic influence on collagen synthesis in the airways and pulmonary ve ssels. Abolition of this influence by denervation may lead to structur al changes analogous to those observed in bronchiolitis obliterans aft er lung transplantation.