Nitric oxide and endothelin-1 in pulmonary hypertension

We have shown previously increased expression of the potent vasoconstrictor peptide endothelin-1 (ET-1) in the pulmonary arteries of patients with pulmonary hypertension. We also demonstrated diminished expression of endothelial nitric oxide synthase, the enzyme responsible for generating nitric oxide (NO), in patients with the same disease.

To determine the expression of neuronal nitric oxide synthase (NOS-I) and endothelin-converting enzyme-1 (ECE-1) in lungs of patients with pulmonary hypertension.

Immunohistochemistry with avidin-biotin-peroxidase method.

There was little immunostaining for NOS-I in the pulmonary arteries of normal control or diseased lungs. Moderate diffuse staining was seen in the airway epithelium and nerve bundles. Immunoreactivity for ECE-1 was seen in the airway epithelium, smooth muscle cells, and scattered macrophages of both normal and diseased lungs. Strong immunoreactivity for ECE-1 was seen in the endothelium of diseased pulmonary arteries of patients with pulmonary hypertension.

We conclude that expression of NOS-I appears to be similar in normal and diseased lungs, while abundant expression of ECE-1 is present in diseased vessels, which may contribute to the pathogenesis of arteriopathy in pulmonary hypertension.