Pulmonary vascular remodeling distal to pulmonary artery ligation is accompanied by upregulation of endothelin receptors and nitric oxide synthase

Exp Lung Res. 2000 Jun;26(4):287-301. doi: 10.1080/019021400404555.


There is increasing evidence that the pathogenesis and progression of many forms of pulmonary vasculopathy are related to abnormalities in endothelial mediators, including endothelin-1 (ET-1) and nitric oxide (NO). Using a rat model of chronic unilateral pulmonary artery ligation, we investigated the role of ET-1 and NO in postobstructive pulmonary vasculopathy (POPV). Eight months after a left thoracotomy with either left main pulmonary artery ligation (ligated group) or no ligation (sham group), rat lungs, including those contralateral to the ligation (hyperperfused group), were fixed and mounted for histologic sectioning. Morphometric measurements were carried out by computer-assisted image analysis and immunohistochemical staining was performed using specific antibodies against ET-1, ETA, and EBB receptors, and endothelial NO synthase (eNOS). Compared to sham lungs, the ligated lungs showed (1) an increase in muscular, adventitial, and intimal thickness of pulmonary artery; (2) increase in external diameter of the bronchial artery (39.8 +/- 2.2 microns vs. 16.8 +/- 0.9 microns in sham group; P < .005) and number of bronchial arteries per bronchiole (3.21 +/- mu 0.26 vs. 1.86 +/- mu 0.21 in sham group; P < .001); and (3) increase in the intensity of eNOS and ETA, B receptor immunoreactivity. No morphometric or immunohistochemical differences were observed between the hyperperfused and sham lungs. These findings suggest that increased synthesis of endothelial NO may serve as a compensatory mediator in ET-1-mediated vascular remodeling.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arterial Occlusive Diseases / metabolism
  • Arterial Occlusive Diseases / pathology
  • Bronchial Arteries / chemistry
  • Bronchial Arteries / pathology
  • Disease Models, Animal
  • Endothelin-1 / immunology
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / pathology
  • Immunohistochemistry
  • Ligation / adverse effects
  • Lung / blood supply
  • Lung / chemistry
  • Lung / pathology
  • Male
  • Nitric Oxide Synthase / immunology
  • Nitric Oxide Synthase / physiology*
  • Pulmonary Artery / chemistry
  • Pulmonary Artery / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Endothelin / immunology
  • Receptors, Endothelin / physiology*
  • Up-Regulation


  • Endothelin-1
  • Receptors, Endothelin
  • Nitric Oxide Synthase