HYPOXIA-REOXYGENATION IMPAIRS ENDOTHELIUM-DEPENDENT RELAXATION IN ISOLATED RAT AORTA

The effects of hypoxia followed by reoxygenation on endothelium-depend ent relaxation in isolated rat aorta were investigated. Acetylcholine (ACh, 3 nM-10 mu M) and calcium ionophore A-23187 (3 nM-300 nM)-induce d endothelium-dependent vasorelaxation of isolated rat aortic vessel r ings was impaired after 15 min of hypoxia followed by 30 min of reoxyg enation. Impairment of ACh-induced relaxation was prevented by pretrea tment with the combination of superoxide dismutase (200 U/ml) and cata lase (1,000 U/ml). Hypoxia-reoxygenation did not affect sodium nitropr usside (0.1 nM-1 mu M)-induced endothelium-independent relaxation nor the dissociation constant of ACh to endothelial M(3) muscarinic recept ors. Propidium iodide staining of the vascular endothelium revealed a significant increase in the number of dead endothelial cells on the ao rtic vessel rings following hypoxia-reoxygenation, but not on those pr etreated with superoxide dismutase and catalase. These results suggest that hypoxia-reoxygenation impairs endothelium-dependent relaxation o f rat aorta by a mechanism that involves oxidant-mediated endothelial cell death.