Cell redox state and hypoxic pulmonary vasoconstriction: recent evidence and possible mechanisms

Abstract

During alveolar hypoxia, hypoxic pulmonary vasoconstriction (HPV) maintains blood oxygenation near optimum via incompletely defined mechanisms. It is proposed that a hypoxia-induced rise in the intracellular concentration of reactive oxygen species (ROS) or an oxidising shift in the cytoplasmic redox state provides the signal which initiates the constriction of pulmonary arteries (PA), although this is controversial. Here, we review recent investigations demonstrating that hypoxia causes a rise in [ROS] in PA smooth muscle, and that ROS and antioxidants have effects on PA which would be predicted if cell oxidation causes contraction. We argue that intracellular Ca2+ release and Ca2+-sensitisation are the key effector mechanisms causing HPV, and discuss evidence that both processes are promoted by ROS or oxidative protein modifications. We conclude that while it is plausible that an increase in cytoplasmic [ROS] activates HPV effector mechanisms, proving this link will require the determination of whether hypoxia causes oxidative modifications of proteins involved in Ca2+ homeostasis and sensitisation.