Endothelial function in clinical pulmonary hypertension.

The endothelium regulates the concentrations of several types of vasoactive substances that affect pulmonary vascular tone, and endothelia can oppose vasoconstriction in some circumstances by releasing vasodilators. To assess some of these endothelial functions in patients with pulmonary hypertension, we made measurements of selected vasoactive substances before and during attempts at pharmacologic vasodilatation. Studies were performed in 16 patients (1 1/2 to 23 years of age) with either idiopathic pulmonary hypertension (n = 11) or pulmonary hypertension as a consequence of unexpected early pulmonary vascular disease accompanying congenital heart defects (n = 5). In six of ten children, norepinephrine levels were elevated, and in two of the six, the concentrations of norepinephrine were greater in the aorta than in the pulmonary artery. In four out of 16 patients, thromboxane levels were increased, and in three of the four, the concentrations of thromboxane were greater in the aorta than in the pulmonary artery. These concentration gradients suggest pulmonary release of these vasoconstrictors. Identification of the contribution to pulmonary vasoconstriction made by changes in the endothelial metabolism of vasoactive substances may lead to a more fundamental understanding of the control of the pulmonary circulation, and hence lead to more specific modes of therapy for pulmonary hypertension.