Site and mechanism of uptake of 3H--norepinephrine by isolated perfused rat lungs.
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Biomedical subjects
Publications and source records attributed to A F Junod.
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The lung is able to rapidly remove 5-hydroxytryptamme (5-HT) from the circulation by a Na(+)-dependent transport mechanism. In order to identify the sites of uptake, radioautographic studies were done on rat lungs which had been isolated and perfused with 5-HT-(3)H and 0 5 mM iproniazid, a monoamine oxidase inhibitor. In control experiments 10(-4)M imipramine was added to the perfusate to inhibit the membrane transport of 5-HT At the light microscope level, silver grains were seen concentrated near capillaries and in the endothelium of large vessels From electron microscope radioautographs a semiquantitative grain count was made and 90% of the silver grains were observed over capillary endothelial cells. The grains were found over the nucleus and cytoplasm of the cell and shewed no preferential association with any particular cytoplasmic inclusion bodies, organelles, or vesicles Other cell types were unlabeled except for a few mast cells, certain vascular smooth muscle cells, and one nerve ending. This radioautographic demonstration of the cell type responsible for the rapid removal of 5-HT from the lung circulation clearly establishes the existence of a new metabolic role for pulmonary endothelial cells.
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A 17-year old boy presented with severe, predominantly central sleep apnoeas secondary to structural damage in the medulla. At low O2 saturation, the electroencephalogram showed the sudden onset of slow waves. Hypercapnic ventilatory response was low and hypoxic ventilatory response was absent. Low flow oxygen therapy dramatically improved the apnoea score, probably by relieving hypoxic brain depression. Slow waves also disappeared with oxygen therapy. Aminophylline was effective on apnoea score and duration (p less than 0.001). This beneficial effect could be explained by an improvement of the normal oscillations of respiration at the onset of sleep, a change in arousability or a stimulation of the ascending reticular system. These findings suggest a possible role of hypoxic depression in the manifestations of central sleep apnoeas and demonstrate the beneficial effect of low flow oxygen and aminophylline in treating certain central sleep apnoeas.
The monovalent reduction of O2 gives rise to highly reactive O2 intermediates, such as superoxide radical (O2-.), hydrogen peroxide (H2O2), and hydroxyl radical (OH.), as well as to singlet O2 (1O2). These O2 metabolites are capable of acting on several groups of substances: enzymes to inactivate them, polyunsaturated fatty acids to form lipid peroxides and DNA to cause single strand breaks and mutations. There are, however, several lines of antioxidant defences, which can be enzymatic (superoxide dismutase, catalase, glutathione peroxidase) or non-enzymatic (glutathione, vitamins C and E, beta-carotene, etc.). These defences are necessary to protect the cell against the intracellular or extracellular generation of O2 metabolites. Since O2 intermediates can affect the general cellular metabolism and inhibit cell replication or reduce protein synthesis, all the biological effects of O2 and its metabolites should therefore be considered in the pathogenesis of emphysematous lesions in the lung.
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