Hypoxia-reoxygenation impairs endothelium-dependent relaxation in isolated rat aorta.
The effects of hypoxia followed by reoxygenation on endothelium-dependent relaxation in isolated rat aorta were investigated. Acetylcholine (ACh, 3 nM-10 microM) and calcium ionophore A-23187 (3 nM-300 nM)-induced endothelium-dependent vasorelaxation of isolated rate aortic vessel rings was impaired after 15 min of hypoxia followed by 30 min of reoxygenation. Impairment of ACh-induced relaxation was prevented by pretreatment with the combination of superoxide dismutase (200 U/ml) and catalase (1,000 U/ml). Hypoxia-reoxygenation did not affect sodium nitroprusside (0.1 nM-1 microM)-induced endothelium-independent relaxation nor the dissociation constant of ACh to endothelial M3 muscarinic receptors. Propidium iodide staining of the vascular endothelium revealed a significant increase in the number of dead endothelial cells on the aortic vessel rings following hypoxia-reoxygenation, but not on those pretreated with superoxide dismutase and catalase. These results suggest that hypoxia-reoxygenation impairs endothelium-dependent relaxation of rat aorta by a mechanism that involves oxidant-mediated endothelial cell death.
Yokoyama
S
S
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130, USA.
Korthuis
R J
RJ
Benoit
J N
JN
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology*; D001667:Binding, Competitive; D000001:Calcimycin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D011976:Receptors, Muscarinic; D009599:Nitroprusside; D000001:Calcimycin; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine; D010100:Oxygen