Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A₂ is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A₂ and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium.

We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A₂ and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls.

The 24-hour excretion of 11-dehydro-thromboxane B₂ (a stable metabolite of thromboxane A₂) was increased in patients with primary pulmonary hypertension and patients with secondary pulmonary hypertension, as compared with normal controls (3224±482, 5392±1640, and 1145±221 pg per milligram of creatinine, respectively; P<0.05), whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F_1α (a stable metabolite of prostacyclin) was decreased (369± 106, 304±76, and 644± 124 pg per milligram of creatinine, respectively; P<0.05). The rate of excretion of all metabolites in the patients with COPD but no clinical evidence of pulmonary hypertension was similar to that in the normal controls.

An increase in the release of the vasoconstrictor thromboxane A₂, suggesting the activation of platelets, occurs in both the primary and secondary forms of pulmonary hypertension. By contrast, the release of prostacyclin is depressed in these patients. Whether the imbalance in the release of these mediators is a cause or a result of pulmonary hypertension is unknown, but it may play a part in the development and maintenance of both forms of the disorder. (N Engl J Med 1992; 327:70–5.)