Simultaneous measurement of O2 radicals and pulmonary vascular reactivity in rat lung.
The role of endogenous radicals in the regulation of pulmonary vascular tone was evaluated by simultaneous measurement of pulmonary artery pressure and lung radical levels during exposure of isolated rat lungs to varying inspired O2 concentrations (0-95%) and angiotensin II. Lung radical levels, measured "on-line" using luminol and lucigenin-enhanced chemiluminescence, decreased in proportion to the degree of alveolar hypoxia. Radical levels fell during hypoxia before the onset of pulmonary vasoconstriction and promptly returned to basal levels with restoration of normoxic ventilation. Mild alveolar hypoxia (10% O2), which failed to decrease chemiluminescence, did not trigger pulmonary vasoconstriction. Although chemiluminescence tended to decrease more as the hypoxic response strengthened, there was not a simple correlation between the magnitude of the change in chemiluminescence induced by hypoxia and the strength of the hypoxic pressor response. Normoxic chemiluminescence was largely inhibited by superoxide dismutase but not catalase. Superoxide dismutase also increased normoxic pulmonary vascular tone and the strength of the pressor response to hypoxia and angiotensin II. Thus the predominant activated O2 species in the lung, during normoxia, was the superoxide anion or a closely related substance. Alteration of endogenous radical levels can result in changes in vascular tone. It remains uncertain whether the decrease in lung radical production during hypoxia caused pulmonary vasoconstriction or was merely associated with hypoxic ventilation.
Archer
S L
SL
Department of Medicine, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Nelson
D P
DP
Weir
E K
EK
D000166:Acridines; D000818:Animals; D000975:Antioxidants; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine; D005609:Free Radicals; D006439:Hemodynamics; D008163:Luminescent Measurements; D008165:Luminol; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion; D011651:Pulmonary Artery / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D013057:Spectrum Analysis; D014661:Vasoconstriction
D000166:Acridines; D000975:Antioxidants; D005609:Free Radicals; C033472:10,10'-dimethyl-9,9'-biacridinium; D008165:Luminol; D002374:Catalase; D003676:Deferoxamine; D010100:Oxygen