Mechanisms of increased vascular permeability associated with sympathetic excitability and the development of treatment strategy of ARDS.

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Diseases such as adult respiratory distress syndrome (ARDS) have increased pulmonary vascular permeability in its entity and treatment strategy is fundamental importance. We have previously reported in the neurogenic pulmonary edema rats that a substance (neuropeptide y: NPY) coexisting with norepinephrine in the sympathetic nerves exerts vascular permeability. We have further elucidated the relationship between NPY and vascular permeability in the present research.1) Abelson tyrosine kinase (Abl) and vascular permeabilityAbl is one of the protein phosphorylation enzymes related with actin polymerization and intranuclear protein synthesis (transcription factor). Non-specific inhibitors of Abl decreased vascular permeability caused by NPY.2) NPY and cell proliferationIt has been reported that vascular endothelial cell proliferation is closely related with vascular permeability. We have shown that in high NPY, hypoxia increased cell proliferation, whereas normal oxygen concentration caused no proliferation. In low NPY, neither hypoxia nor normal oxygen concentration caused proliferation. As in increased vascular permeability, NPY increased vascular cell proliferation by activation of phospholipase C through protein G and activations of protein kinase C and calmodulin-dependent phosphrylation enzyme.3) Cloning of NPY Y_3 receptorWe have found that the increased proliferation of vascular endothelial cells in hypoxia in the presence of NPY was through NPY Y_3 receptor as was found in increased vascular permeability. However, NPY Y_3 receptor is the only subtype of NPY which has unknown amino acids arrangement. In the NPY Y3 receptor, there would be a chance of transformation of the NPY Y_2 receptor.