ABSTRACT
Hypoxic pulmonary vasoconstriction is a distinctive physiologic reaction of the pulmonary vasculature that is initiated by the pulmonary arterial smooth muscle cells as an acute response to changes in environmental O2 tension. While the contractile response of the myocytes is mediated through the coordinated engagement of cellular Ca++ and K+ channels, the ultimate O2 sensor resides within the mitochondrial electron transport chain. Evidence is presented for the divergent theories that have emerged as to the precise identity of this sensor and the corresponding nature of the mitochondrial hypoxic response. Despite these ongoing questions, reactive oxygen species (ROS) are widely recognized as vital messengers in redox-dependent signaling relays between the mitochondrial ETC and downstream effectors during hypoxic states. Under conditions of sustained hypoxia, the same mitochondrial sensing and signaling pathways are implicated in chronic vascular adaptations and the emergence of hypoxic pulmonary hypertension through the activation of O2-sensitive transcription factors. Other sources of ROS and antioxidant mechanisms are recognized as important potential modifiers of these redox-based cellular signals.
