PARADOXIC PULMONARY VASOCONSTRICTION IN RESPONSE TO ACETYLCHOLINE IN PATIENTS WITH PRIMARY PULMONARY-HYPERTENSION

Pulmonary vascular reactivity was assessed during diagnostic heart cat heterization in two patients with pulmonary hypertension unexplained b y pulmonary or cardiac disease and in five patients with atypical ches t pain and normal coronary arteriograms. Acetylcholine, an endothelium -dependent vasodilator that also has a direct contracting effect on va scular smooth muscle cells, was infused in the right atrium in a step- wise increasing dose in order to obtain final blood concentrations in the pulmonary circulation ranging from 10(-6) mol/L to 10(-4) mol/L. I n the five control patients, acetylcholine induced a dose-related decr ease of pulmonary vascular resistance (-52 percent +/-9 percent). In t he patients with primary pulmonary arterial hypertension, however, ace tylcholine caused a paradoxic increase of pulmonary arterial pressure and of pulmonary vascular resistance. Thus, it appears that endotheliu m-dependent vasodilation is impaired in the pulmonary circulation of p atients with primary pulmonary arterial hypertension. Endothelial dysf unction in the pulmonary circulation may play a role in the pathophysi ology of this disease.