M. Albertini et Mg. Clement, HYPOXIC PULMONARY VASOCONSTRICTION IN PIGS - ROLE OF ENDOTHELIN-1, PROSTANOIDS AND ATP-DEPENDENT POTASSIUM CHANNELS, Prostaglandins, leukotrienes and essential fatty acids, 59(2), 1998, pp. 137-142
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.