الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 141 |  |  |
| | | from | 141 | | |
Abstract
Pulmonary hypertension is an incurable, progressive disease, characterized by pulmonary arterial remodeling that can be induced by chronic hypoxic exposure. Three main changes occur in mammals in response to low oxygen; pulmonary smooth muscle vasoconstriction, carotid body chemoreceptor-induced hyperventilation, and chronic cellular hypoxia inducible factor (HIF) mediated activation of key downstream targets. Mitochondrial reactive oxygen species (ROS) have been implicated in disease development of hypoxia-induced PH possibly via stabilization of the hypoxia-inducible factor-1 (HIF-1).
In our study we showed that scavenging mitochondrial superoxide by mitoTEMPO treatment, in vivo, did not reverse the development of chronic hypoxia-induced pulmonary hypertension, because our results together with previous findings, at least under particular conditions, showed that adaptation of cellular metabolism causes decreased ROS concentration in chronic hypoxia compared with acute hypoxia. As well the previous controversies regarding the role of ROS in acute and chronic PH may be based on the fact that ROS have both location-dependent and concentration-dependent and species-specific effects.
Moreover, our study revealed that HIF-1α stabilization is a time and cell type specific. Mitochondrial ROS inhibition by mitoTEMPO treatment and application of exogenous H2O2 did not affect HIF-1α stabilization at least under these condition.