HYPOXIC PULMONARY VASOCONSTRICTION IN PIGS - ROLE OF ENDOTHELIN-1, PROSTANOIDS AND ATP-DEPENDENT POTASSIUM CHANNELS

This study investigated the mechanisms that may contribute to the hypo xic pulmonary vasoconstriction and compared the effects of hypoxia on pulmonary and systemic vascular beds. Six anesthetized spontaneously b reathing pigs inhaled a hypoxic mixture (10% O-2 in air) in control co nditions and after pre-treatment with Indomethacin (3 mg kg(-1) i.v.) to block the cyclooxygenase pathway. During hypoxia, the Indomethacin pre-treated pigs were given Cromakalim (80 mu g kg(-1) i.v.) to activa te K-ATP(+) channels. Bosentan (5 mg kg(-1) i.v.) was administered to block endothelin-1 receptors and then during hypoxia Cromakalim was ad ministered as before. In all experimental conditions we recorded breat hing pattern and vascular parameters: mean systemic and pulmonary arte rial pressures;systemic and pulmonary vascular resistances; cardiac ou tput; and heart rate. Vascular and respiratory responses to hypoxia we re determined when PaO2 was reduced to 50 +/- 5 mmHg. The main finding was that in spontaneously breathing pigs, hypoxia induces pulmonary v asoconstriction and an increase in mean systemic arterial pressure, wh ich are cyclooxygenase-independent. A role of endothelin-1 appears in both vascular districts, but pulmonary vasoconstriction may also be du e to ET-1-dependent inhibition of K-ATP(+) channels.