The 187th Meeting of the Pathological Society of Great Britain and Ireland, The Robin Brook Centre, St. Bartholomew's Hospital, London, 6–7 January 2005

We determined the hepatic expression of transcriptional factor HIF-1α inhypoxia and genes possessing hypoxia response element (HRE) such as iNOS,VEGF and ET-1 that modulate the vascular response in liver. We also evaluatedthe concomitant expressions of NF-κB and AP-1. Blood and liver samples fromadult SD rats were collected at specific time-points after exposure of animals to10% oxygen for a period of 28 days. Samples from the normoxic and hypoxicrats were analyzed for serum ALT, hematocrit, 8-isoprostane,immunohistochemistry, RT-PCR, Western Blotting and EMSA.Our results showed a significant increase in the hematocrit and asignificant weight loss in the hypoxic rats. The liver morphology and serumALT were normal. Total free 8-isoprostane levels and nitrotyrosine proteinwere not elevated. iNOS mRNA peaked at day 21 whereas eNOS, VEGF andET-1 mRNAs progressively increased from day 7 to day 28 in hypoxic liver.Similar trends were observed at the protein level by Western blotting. HIF-1α,NF-κB and AP-1 were upregulated in hypoxic liver. We conclude that thevascular adaptive ability of the liver in chronic hypoxia triggers compensatorynitric oxide-dependent mechanisms for cell survival towards a vasodilatoryresponse through upregulation of transcription factors, HRE and eNOS geneslink_to_subscribed_fulltex