Potential mechanism of vasomotor dysregulation after lung transplantation for primary pulmonary hypertension.
BACKGROUND
Vasomotor regulation in the lung is controlled by a dynamic balance between humoral factors and autonomic innervation. Lung transplantation 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 life-threatening hypoxemia was dramatically reversed with the administration of organic nitrates. The potential mechanism for this dysregulation was explored by exposing human endothelial cells to hypoxic conditions in vitro and analyzing the cells for the expression of pulmonary vasoconstrictor gene transcripts.


RESULTS
The hypoxic microenvironment induced a tenfold increase in the transcription of the pulmonary vasoconstrictor genes endothelin-1 and platelet-derived growth factor within 24 hours. The addition of organic nitrates had a dramatic effect on decreasing the levels of vasoconstrictor transcripts within 30 minutes of exposure.


CONCLUSIONS
These findings suggest that a potential mechanism for the clinical effect of organic nitrates is the inhibition of vasoconstrictor synthesis by hypoxic endothelium.
Mentzer
S J
SJ
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Reilly
J J
JJ
DeCamp
M
M
Sugarbaker
D J
DJ
Faller
D V
DV
D000328:Adult; D002478:Cells, Cultured; D016232:Endothelins / Q000096:biosynthesis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery*; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D009599:Nitroprusside / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic
D016232:Endothelins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D009599:Nitroprusside