Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 7)

Although our conclusion on the importance of LT in development of LPS-induced lung injury is based only on indirect evidence, ie, inhibition of sLT synthesis, it is strongly supported by the following. First, during sepsis LT concentration in lungs is always increased . Second, administration of exogenous sLT (LTC4, LTD4, LTE4) produces in lungs a shock-like state consisting of constriction of bronchi and lung parenchyma, stimulation of vascular smooth muscle and increase in pulmonary artery pressure with subsequent reductions in regional blood flow and promotion of vascular leakage of fluid into the lungs . LTB4 may aggravate the effects of smooth muscle vasoconstriction by trapping leukocytes and macrophages in the microcirculation, further reducing blood flow to the lungs and other organs . Finally, LPS-induced shock can be ameliorated by LT synthesis inhibitors other than BAY X1005 or by LT receptor antagonists .

Recently it became clear that the formation of LT is not limited to cells that contain 5-lipoxygenase and FLAP (eg, leukocytes and macrophages) , and that LTA4 can also be converted to LTB4 and sLT in red blood cells, platelets , endothelial cells and smooth muscle cells that are deficient in 5-lipoxygenase and FLAP but have large quantities of LTA4 hydrolase or LTC4 synthase. Folco’s group presented in vitro and in vivo evidence that endothelium of coronary vessels can synthesize sufficient sLT from PMNL-derived LTA4. Also, in our experiments LPS-induced formation of sLT in the lung did not seem to depend on the lung tissue alone because, in contrast with blood-perfused lung, lung perfused with Krebs-buffered LPS does not produce an increase in PAP with subsequent injury to the lung tissue. Online shopping will cost you less money and will take less time, because you can find efficient Claritin online tablets with generous discounts at the pharmacy that proved its reputability and desire to help by offering best level of service and most efficient drugs.

This entry was posted in Lung injury and tagged BAYX1005, Leuko-trienes, Leukotriene synthase inhibitors, Lipopolysaccharide, Lung injury, Septic shock.