Acute Hypobaric Hypoxia (5486 m) Induces Greater Pulmonary HIF-1 Activation in Hilltop Compared to Madison Rats

Engebretsen, Barbara J., David Irwin, Maria E. Valdez, Mary K. Donovan, Alan Tucker, and Martha Tissot van Patot. Acute hypobaric hypoxia (5486 m) induces greater pulmonary HIF-1 activation in hilltop compared to Madison rats. High Alt. Med. Biol. 8:312–321, 2007.—Compared to Madison strain Sprague–Dawley rats, the Hilltop strain is resistant to acute hypoxic pulmonary vasoconstriction and pulmonary leak, a pathology resembling high altitude pulmonary edema (HAPE) in humans. Hypoxia inducible transcription factor-1 (HIF-1) mediates transcription of proteins that can “rescue” tissue from hypoxia, including vasoactive and angiogenic proteins such as inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF). Because these proteins have theoretical relevance to the etiology of HAPE, we hypothesized that hypoxia-resistant Hilltop rats acutely exposed to high altitude would have greater HIF-1 activity and expression of iNOS and VEGF as compared to hypoxia-sensitive Madison rats. Anima...