thromboxane-a2 and Hyperventilation

This study was designed to test the hypothesis that hyperventilation-induced bronchoconstriction (HIB) results from the combined effects of prostanoid and leukotriene metabolism. A bronchoscope was used in anesthetized dogs to record peripheral airway resistance and HIB before and after combined treatment with inhibitors of cyclooxygenase (indomethacin) and 5-lipoxygenase (MK-0591). Bronchoalveolar lavage fluid (BALF) cells and mediators from hyperventilated and control airways were also measured. Pretreatment with MK-0591 and indomethacin significantly attenuated, but did not abolish, HIB. However, addition of atropine nearly eliminated the residual response. Blockade of eicosanoid metabolism markedly reduced the concentrations of eicosanoids recovered in BALF after hyperventilation. Positive correlations between posthyperventilation BALF prostanoid and epithelial cell concentrations are suggestive of mucosal injury-induced mediator production and release. We conclude that HIB is prevented in the presence of eicosanoid and muscarinic-receptor blockade and that both classes of eicosanoids contribute similarly to the development of HIB.

Topics: Animals; Arachidonate 5-Lipoxygenase; Asthma; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cyclooxygenase Inhibitors; Dinoprost; Dogs; Eicosanoids; Epithelial Cells; Hyperventilation; Indomethacin; Leukotrienes; Male; Muscarinic Antagonists; Receptors, Muscarinic; Thromboxane A2

The influence of hyperventilation on the spontaneous generation of prostacyclin and thromboxane A2 by isolated rat lungs was studied. Both prostacyclin and thromboxane A2, as measured by RIA of their stable end-products, 6-oxo-PGF1 alpha and TXB2 respectively, were continuously released into the perfusate. However, the concentration of prostacyclin in the perfusate was higher than thromboxane A2. Under normal ventilation at a rate 40-50 breaths/min, the ratio between these two compounds was 5:1. Increasing the rate of respiration to 100 breaths/min preferentially stimulated the release of prostacyclin. During hyperventilation-stimulated release of prostacyclin and thromboxane A2. Hydroperoxy-fatty acids and tranylcypromine inhibited only the release of prostacyclin but did not affect the generation of thromboxane A2. Our findings confirm that the lung generates prostacyclin predominantly, and provide direct evidence that respiratory movements are involved in generation of pulmonary prostacyclin and thromboxane A2.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Aspirin; Epoprostenol; Fatty Acids; Hyperventilation; Indomethacin; Lung; Male; Prostaglandins; Prostaglandins F; Rats; Thromboxane A2; Thromboxanes; Tranylcypromine