Abstract
Increase in pulmonary vascular permeability by oxygen free radicals derived from neutrophils participates deeply in the pathophysiology of acute lung injury such as ARDS. Cyclic AMP restrains hyperpermeability of pulmonary vasculature in previous studies using? isolated perfused lungs, and endothelial cell monolayers. Cyclic GMP is also supposed to have the similar action. Atrial natriuretic peptide (ANP) increases intracellular cGMP content through a receptor on the cell surface. ANP is applied for the treatment of a heart failure, because its Na-diuretic effect and dilating effect on blood vessel reduce prelord and afterload of the heart. We paid attention for ANP to increase intracellular cGMP content and examined the action of ANP to inhibit H2O2-induced hyperpermeability of pulmonary vasculature. We used isolated perfused lungs of rabbit, and H2O2 was administered at dose of 100 μM, 200 μM, 500 μM. Left atrial pressure (Pla), pulmonary artery pressure (Ppa) and lung weight gain (ΔW) were measured. Pulmonary capillary pressure was also measured with a double occlusion method and capillary filtration coefficient (Kfc) was calculated using a Paul's method. ΔW and Kfc were significantly increased dose-dependently after H2O2 administration (p <0.05) . Increase of ΔW, Kfc and Ppa were significantly attenuated (p <0.05) by ANP. These results suggest that ANP attenuates the H2O2-induced hyper-permeability of pulmonary vascular and ANP is a useful therapeutic agent for the patient with hyperpermeability lung edema.
