Mitochondrial Complex II is Essential for Hypoxia-induced ROS Generation and Vasoconstriction in the Pulmonary Vasculature

Abstract

In the pulmonary vasculature hypoxia induces vasoconstriction and vascular remodelling. By directing the blood flow away from poorly ventilated regions of the lung perfusion is matched to ventilation. However, persistent activation of these mechanisms causes pulmonary hypertension. Up to now both the molecular structure of the oxygen sensor and the subsequent signalling cascade are still under debate. A role as early mediator of the hypoxic response is discussed for reactive oxygen species (ROS). However, the data presented in the literature about the hypoxic regulation of ROS generation are controversial. The aim of our study was to investigate the production of ROS by cells of small intrapulmonary arteries under conditions of normoxia and hypoxia. The source of normoxic and hypoxic ROS generation was characterized by application of inhibitors of the individual complexes of the mitochondrial respiratory chain. Additionally, the requirement of functional mitochondrial complex II for hypoxic pulmonary vasoconstriction was determined by videomorphometric analysis of small intrapulmonary vessels in precision cut lung slices.