Reduced Expression of Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension

doi:10.1056/NEJM199507273330403

Volume 333:214-221		July 27, 1995		Number 4

Reduced Expression of Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension

Adel Giaid, Ph.D., and Dina Saleh, B.Sc.

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ABSTRACT

Background Pulmonary hypertension is characterized by abnormalthickening of the pulmonary arteries and increased pulmonaryvascular resistance. Nitric oxide is a potent endothelium-derivedvasorelaxant substance and an inhibitor of smooth-muscle-cellgrowth. Nitric oxide is produced in various cell types by theaction of an enzyme, nitric oxide synthase. We compared theexpression of endothelial nitric oxide synthase in the lungsof control subjects with that in the lungs of patients withpulmonary hypertension.

Methods We investigated the expression of endothelial nitricoxide synthase by histochemical and immunohistochemical analysis,in situ hybridization, and Northern blot analysis in the lungsof 22 patients with plexogenic pulmonary arteriopathy (arteriopathyof grades 4 through 6), 24 patients with secondary pulmonaryhypertension (arteriopathy of grades 1 through 3), and 23 controlsubjects.

Results In the lungs of the control subjects, nitric oxide synthasewas expressed at a high level in the vascular endothelium ofall types of vessels and in the pulmonary epithelium. In contrast,little or no expression of the enzyme was found in the vascularendothelium of pulmonary arteries with severe histologic abnormalities(i.e., plexiform lesions) in patients with pulmonary hypertension.The intensity of the enzyme immunoreactivity correlated inverselywith the severity of histologic changes. There was an inversecorrelation between the arterial expression of the enzyme andtotal pulmonary resistance in patients with plexogenic pulmonaryarteriopathy (r = -0.766, P = 0.004).

Conclusions Pulmonary hypertension is associated with diminishedexpression of endothelial nitric oxide synthase. It is possiblethat decreased expression of nitric oxide synthase may contributeto pulmonary vasoconstriction and to the excessive growth ofthe tunica media observed in this disease.

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From the Department of Pathology, Montreal General Hospital, and McGill University, Montreal.

Address reprint requests to Dr. Giaid at the Department of Pathology, Montreal General Hospital, 1650 Cedar Ave., Montreal, QC H3G 1A4, Canada.

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Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension
Xue C., Johns R. A., Giaid A., Saleh D.
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N Engl J Med 1995; 333:1642-1644, Dec 14, 1995. Correspondence

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