Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary circulation but the mechanism remains elusive. Red blood cells (RBCs) are known to augment HPV and to release more ATP as oxygen content falls. Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. Hence we hypothesized that ATP and leukotrienes are mediators of HPV produced during acute alveolar hypoxia.

In forty Sprague-Dawley rats, lungs were isolated and perfused. We administered ATP (10 µM) to the ATP group (n = 8), the ATP antagonist, suramin (100 µM) to the suramin group (n = 8), leukotriene C₄ (LTC₄, 5 µg) to the LTC₄ group (n = 8), the LTC₄ antagonist, LY171883 (20 µM) to the LY171883 group (n = 8), and LTC₄ (5 µg) + ATP (10 µM) to the LTC₄ + ATP group (n = 8) during normoxic ventilation. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. Baseline pulmonary artery pressure change after exposure to each drug and hypoxic pressor response between a period 21% normoxic gas ventilation and that of 3% hypoxic gas ventilation were measured.

ATP and LTC₄ + ATP increased baseline pulmonary artery pressures but LTC₄ did not alter it. ATP did not affect hypoxic pressor response. Suramin, LY171883 and LTC₄ + ATP inhibited the pressor response to hypoxia. LTC₄ increased hypoxic pressor response.

In isolated rat lungs, HPV may be mediated by ATP and LTC₄ appears more likely to be a modulator than a mediator of HPV.