EFFECTS OF HYPOXIA, MECHANICAL AND CHEMICAL ENDOTHELIUM DENUDATION ON GUINEA-PIG ISOLATED PULMONARY-ARTERIES

1. The isolated unstimulated main trunk, extralobar and intralobar branches of the pulmonary artery of the guinea-pig developed well-sustained contractions upon exposure to hypoxia (95% N-2-5% CO2 gas mixture; P-O2 11-15 mm Hg). The contractions were readily reversible by reoxygenation (95% O-2-5% CO2). 2. Mechanical removal of the endothelium did not significantly affect the magnitude of the hypoxia-induced contractions in rings obtained from the main trunk of the pulmonary artery but reduced those of rings obtained from the proximal and distal extralobar branches. 3. Mechanical removal of the endothelium also did not affect the magnitude of contractions induced by BaCl2 in the main but significantly reduced contractions induced by the same agent in the proximal and distal extralobar branches of the pulmonary artery, suggesting that the reduction of hypoxia-induced contractions in the endothelium-denuded rings is due to impairment of vascular reactivity. 4. Pretreatment with L-N-nitro arginine, an inhibitor of the synthesis of the endothelium-derived relaxing factor, did not significantly affect the hypoxia-induced contractions but increased the magnitude of BaCl2-induced contractions in the main and the extralobar branches. 5. These observations demonstrate that isolated pulmonary artery rings of the guinea-pig develop slow contractions in response to hypoxia without prior contraction with an agonist, and that the endothelium plays little role in the hypoxia-induced contractions of guinea-pig isolated large pulmonary arteries. 6. Furthermore, these observations suggest that the effect of mechanical endothelium denudation or pharmacological manipulation, such as EDRF inhibition, on vascular reactivity should be considered when the effect of hypoxia is studied in isolated pulmonary arteries.