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Skin plays an essential role, mediated in part by its remarkable vascular plasticity, in adaptation to environmental stimuli. Certain vertebrates, such as amphibians, respond to hypoxia in part through the skin; but it is unknown whether this tissue can influence mammalian systemic adaptation to low oxygen levels. We have found that epidermal deletion of(More)
Factor inhibiting HIF-1alpha (FIH) is an asparaginyl hydroxylase. Hydroxylation of HIF-alpha proteins by FIH blocks association of HIFs with the transcriptional coactivators CBP/p300, thus inhibiting transcriptional activation. We have created mice with a null mutation in the FIH gene and found that it has little or no discernable role in mice in altering(More)
Avian pulmonary capillaries differ from those of mammals in three important ways. The blood-gas barrier is much thinner, it is more uniform in thickness, and the capillaries are far more rigid when their transmural pressure is altered. The thinness of the barrier is surprising because it predisposes the capillaries to stress failure. A possible mechanism(More)
When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after(More)
Howlett, Richard A., Norberto C. Gonzalez, Harrieth E. Wagner, Zhenxing Fu, Steven L. Britton, Lauren G. Koch, and Peter D. Wagner. Selected Contribution: Skeletal muscle capillarity and enzyme activity in rats selectively bred for running endurance. J Appl Physiol 94: 1682–1688, 2003. First published December 13, 2002; 10.1152/japplphysiol.00556.2002.—To(More)
Flying requires enormous energy and some birds have higher mass-specific maximal oxygen consumptions than any mammal. The bird lung is very efficient partly because of an extremely thin blood-gas barrier so that some birds have thinner barriers than any mammals. We show here that in addition to the total barrier being very thin, the interstitium which is(More)
Previous physiological studies suggest that avian pulmonary capillaries behave like almost rigid tubes. We made morphometric measurements to determine the diameter of the capillaries in chicken lungs when the transmural pressure was altered over a wide range. The diameter of avian pulmonary capillaries increased by only 13% when the pressure inside them was(More)
The lungs of domestic chickens were perfused with blood or dextran/saline and the pulmonary artery pressure (P(a)) and venous pressure (P(v)) were varied in relation to air capillary pressure (P(A)). In Zone 3 conditions, pulmonary vascular resistance (PVR) was virtually unchanged with increases in either P(a) or P(v). This is very different behavior from(More)
Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in ventilation and ventilatory O2-sensitivity that involves plasticity in carotid body chemoreceptors and CNS respiratory centers. Hypoxia inducible factor-1alpha (HIF-1alpha) controls the expression of several genes that increase physiological O2 supply. Studies using transgenic mice(More)