Janus-faced signaling of cGMP in acute lung injury
نویسندگان
چکیده
The effect of increasing pulmonary endothelial cGMP concentration on endothelial function in acute lung injury appears to depend on 1) the presence of specific cGMP targets, 2) intracellular cGMP compartmentalization and 3) the timing of the increase in cGMP relative to the injury onset [1-4]. For example, we recently showed that pretreatment of pulmonary artery endothelial monolayers with 8pCPT-cGMP attenuated oxidant-induced barrier dysfunction by a cGMP-dependent kinase-1 (cGKI)-dependent mechanism [1,2]. More recently, however, we found that the increase in endogenous lung cGMP resulting from increased NO production in a ventilator-induced lung injury (VILI) mouse model caused lung endothelial barrier dysfunction [4]. The injurious effect of sGC-derived cGMP in VILI was mediated by the simultaneous generation of phosphodiesterase 2A (PDE2A), which was stimulated by cGMP to hydrolyze cAMP. Interestingly, in the same model, pretreatment with BAY 41-2272 (1.5 μM) to stimulate sGC before injurious tidal volume ventilation attenuated VILI.
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