We reasoned that the increase in cardiac mass and work would require an increase in vascularization to supply the myocardium with adequate perfusion. Capillary morphometry demonstrated significant increases in the mean capillar) density, minimal capillary diameter, and capillary: myocardial volume ratio and a significant decrease in intercapillary distance in the hearts of six anemic compared […]

Molecular Physiology: Hypoxia, HIF-1, VEGF, and Vascularization Analysis of the human, mouse and rat VEGF genes revealed the presence of a hypoxia response element in the -flanking region of the gene approximately 1 kb upstream of the transcription start site. The following evidence indicated that HIF-1 activated VEGF transcription in hypoxic cells: (1) forced expression […]

To determine the relationship between 02 concentration and HIF-1 expression, human HeLa cells were exposed to 20%, 14%, 12%, 10%, 8%, 6%, 4%, 2%, or 0.5% 02 for 4 h in a tonometer either in the absence or presence of 1 mM potassium cyanide to block oxidative phosphorylation and eliminate 02 consumption and any extracellular or intracellular 02gradients […]

Forced expression of recombinant HIF-la and HIF-1 p in tissue culture cells resulted in a marked increase in transcription of reporter genes containing a wild-type 50-bp hypoxia-response element from the human EPO gene in cells exposed to 20% 02 and a superinduction in cells exposed to 1% 02. A mutation in the HIF-1 binding site […]

HIF-1 was originally identified as a nuclear factor that was induced by hypoxia and bound to a site in the EPO hypoxia-response element. Nucleotide substitutions in the hypoxia-response element that eliminated HIF-1 binding also eliminated transcriptional activation in response to hypoxia. HIF-1 DNA-binding activity was shown to be tightly regulated by cellular 02 tension. Biochemical […]

Hypoxia can also occur as a local disorder in the context of ischemia due to hypoperfusion, most notably of the cerebral and coronary circulations. When hypoxia is local and vascular in nature, a variety of vasoactive molecules are produced that function either to increase flow through existing vessels (vasodilation) or to promote the growth of […]

From Molecular Biology to Cardiopulmonary Physiology Hypoxia-inducible factor 1 (HIF-1) accumulates in the nuclei of mammalian cells exposed to reduced 02 tension in a time- and 02 concentration-dependent manner. HIF-1 plays an important role in 02 homeostasis by activating transcription of genes whose products mediate essential cellular and systemic responses to hypoxia, including erythropoiesis (erythropoietin), […]

On the one hand, it is relatively easy to envision how a vigorous hypoxic response can be useful in an accidental hypoxic encounter occasioned by ascent or the misfortune of disease; but it is somewhat more difficult to account for the association of a low hypoxic response with prowess in endurance athletic events or with the […]

Further, in contrast to the behavior of low-altitude species, in which hypoxia produces right shifts in oxygen hemoglobin dissociation curve, the bai-headed goose and llama show strongly left-shifted curves. This presumably aids in oxygen loading in the lung but presents a potential disadvantage for its unloading in peripheral tissue. In low-altitude individuals, such left-shifting of […]

To this point, the information presented suggests that a brisk hypoxic ventilatory response may be advantageous with respect to adaptation to hypoxia, as illustrated by the association of a vigorous hypoxic ventilatory response with better performance and fewer symptoms following ascent to high altitude and better maintenance of ventilation in patients with COPD. However, this […]