Prostacyclin has potent vasodilatory, antiaggregatory, antiinflammatory, and antiproliferative properties. In severe human pulmonary hypertension, the lung is deficient in PGI2-synthase. The overall goal of the planned research is to gather critical information required to understand the etiology of the PGI2 synthase impairment of pulmonary hypertensive vessels. The knowledge gained may lead to new, rational treatment strategies for severely hypertensive patients. The current proposal will examine strategies leading to increased PGI2 synthesis via gene therapy. The idea will be tested that mice which overexpress PGI2 synthase in a lung specific manner develop less pulmonary hypertension after exposure to hypoxia than their wild-type counterparts. Lung endothelial cells and airway cells of rats also will be transfected with the PGI2 synthase gene and their response to hypoxia examined.