Antioxidants prevent depression of the acute hypoxic ventilatory response by subanaesthetic halothane in men (original) (raw)

2002, The Journal of Physiology

A major defence of the mammalian body to acute hypoxia is a rapid increase in pulmonary ventilation called the acute hypoxic response (AHR). This vital chemoreflex is primarily mediated by the carotid bodies located at the bifurcations of the common carotid arteries (Gonzalez et al. 1994). During the past decade, considerable progress has been made in unravelling the cascade of events within carotid body type I cells upon exposure to a hypoxic environment, although there are still many areas of controversy (Gonzalez et al. 1994; Lopez-Barneo et al. 2001). The general picture emerging from most studies is that low oxygen decreases the open probability of potassium channels, which causes membrane depolarization and influx of Ca 2+ ions. In several species, various types of potassium channels are described that may serve as an oxygen-sensing element to initiate the transduction cascade in hypoxia, for example, K v channels in rabbits (Perez-Garcia & Lopez-Lopez, 2000; Perez-Garcia et al. 2000) and maxi-K and TASK channels in rats (Buckler et al. 2000; Riesco-Fagundo et al. 2001). Although potassium channels possess redox sensitivity and are sensitive to changes in the concentration of reactive oxygen species (ROS), it is unclear by which mechanism low oxygen is able to decrease the conductance of these channels (Kourie, 1998; Lopez-Barneo et al. 1999; Kobertz et al. 2000). Volatile anaesthetics, e.g. halothane, can open potassium channels in various cell types, such as TASK channels in rat carotid body (Patel et al. 1999; Buckler et al. 2000; Sirois et al. 2000; Patel & Honore, 2001a,b). At the same time, volatile anaesthetics, particularly halothane, are known to depress the acute hypoxic response, an effect that may be mediated through a preferential and potent action on the carotid bodies (Knill & Clement, 1984; Dahan et al. 1994).