POTENTIAL MECHANISM OF VASOMOTOR DYSREGULATION AFTER LUNG TRANSPLANTATION FOR PRIMARY PULMONARY-HYPERTENSION

Background: Vasomotor regulation in the lung is controlled by a dynami c balance between humoral factors and autonomic innervation. Lung tran splantation is a unique clinical situation in which vasoregulation is dependent on humoral factors alone. Methods: We illustrate the problem of vasomotor dysregulation with a lung transplant recipient in whom l ife-threatening hypoxemia was dramatically reversed with the administr ation of organic nitrates. The potential mechanism for this dysregulat ion was explored by exposing human endothelial cells to hypoxic condit ions in vitro and analyzing the cells for the expression of pulmonary vasoconstrictor gene transcripts. Results: The hypoxic microenvironmen t induced a tenfold increase in the transcription of the pulmonary vas oconstrictor genes endothelin-1 and platelet-derived growth factor wit hin 24 hours. The addition of organic nitrates had a dramatic effect o n decreasing the levels of vasoconstrictor transcripts within 30 minut es of exposure. Conclusion: These findings suggest that a potential me chanism for the clinical effect of organic nitrates is the inhibition of vasoconstrictor synthesis by hypoxic endothelium.