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

1. The isolated unstimulated main trunk, extralobar and intralobar bra nches of the pulmonary artery of the guinea-pig developed well-sustain ed contractions upon exposure to hypoxia (95% N-2-5% CO2 gas mixture; P-O2 11-15 mm Hg). The contractions were readily reversible by reoxyge nation (95% O-2-5% CO2). 2. Mechanical removal of the endothelium did not significantly affect the magnitude of the hypoxia-induced contract ions in rings obtained from the main trunk of the pulmonary artery but reduced those of rings obtained from the proximal and distal extralob ar branches. 3. Mechanical removal of the endothelium also did not aff ect the magnitude of contractions induced by BaCl2 in the main but sig nificantly reduced contractions induced by the same agent in the proxi mal 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. Pretrea tment with L-N-nitro arginine, an inhibitor of the synthesis of the en dothelium-derived relaxing factor, did not significantly affect the hy poxia-induced contractions but increased the magnitude of BaCl2-induce d contractions in the main and the extralobar branches. 5. These obser vations demonstrate that isolated pulmonary artery rings of the guinea -pig develop slow contractions in response to hypoxia without prior co ntraction with an agonist, and that the endothelium plays little role in the hypoxia-induced contractions of guinea-pig isolated large pulmo nary arteries. 6. Furthermore, these observations suggest that the eff ect of mechanical endothelium denudation or pharmacological manipulati on, such as EDRF inhibition, on vascular reactivity should be consider ed when the effect of hypoxia is studied in isolated pulmonary arterie s.