Reactive Oxygen Species and Cell Signaling in Lung Ischemia.

This chapter presents a new paradigm for the response to ischemia in the pulmonary circulation. The ischemic response depends on the sensing of decreased shear stress by the endothelial cell, resulting in the activation of membrane-associated NADPH oxidase, generation of O2−, and activation of a signaling cascade. The initial response of the endothelium leading to NADPH oxidase activation is depolarization of the endothelial cell membrane, possibly a result of inactivation of membrane KATP channels (KIR 6.2). ROS signaling leads to NO generation and cell proliferation. Thus, the KATP channel may function as a "flow sensor" with the ability to initiate signaling subsequent to flow cessation. This response to altered shear stress may represent a physiological attempt to promote both vasodilation and the generation of new capillaries as mechanisms to restore blood perfusion. [ABSTRACT FROM AUTHOR]