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The ability to respond rapidly to changes in oxygen tension is critical for many forms of life. Challenges to oxygen homeostasis, specifically in the contexts of evolutionary biology and biomedicine, provide important insights into mechanisms of hypoxia adaptation and tolerance. Here we synthesize findings across varying time domains of hypoxia in terms of oxygen delivery, ranging from early animal to modern human evolution and examine the potential impacts of environmental and clinical challenges through emerging multi-omics approaches. We discuss how diverse animal species have adapted to hypoxic environments, how humans vary in their responses to hypoxia (i.e., in the context of high-altitude exposure, cardiopulmonary disease, and sleep apnea), and how findings from each of these fields inform the other and lead to promising new directions in basic and clinical hypoxia research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Non, Heinrich, Gu, Alcock, Moya, Lawrence, Tift, O'Brien, Storz, Signore, Khudyakov, Milsom, Wilson, Beall, Villafuerte, Stobdan, Julian, Moore, Fuster, Stokes, Milner, West, Zhang, Shyy, Childebayeva, Vázquez-Medina, Pham, Mesarwi, Hall, Cheviron, Sieker, Blood, Yuan, Scott, Rana, Ponganis, Malhotra, Powell and Simonson.) more...

Animal models are useful to understand the myriad physiological effects of hypoxia. Such models attempt to recapitulate the hypoxemia of human disease in various ways. In this mini-review, we consider the various animal models which have been deployed to understand the effects of chronic hypoxia on pulmonary and systemic blood pressure, glucose and lipid metabolism, atherosclerosis, and stroke. Chronic sustained hypoxia (CSH)-a model of chronic lung or heart diseases in which hypoxemia may be longstanding and persistent, or of high altitude, in which effective atmospheric oxygen concentration is low-reliably induces pulmonary hypertension in rodents, and appears to have protective effects on glucose metabolism. Chronic intermittent hypoxia (CIH) has long been used as a model of obstructive sleep apnea (OSA), in which recurrent airway occlusion results in intermittent reductions in oxyhemoglobin saturations throughout the night. CIH was first shown to increase systemic blood pressure, but has also been associated with other maladaptive physiological changes, including glucose dysregulation, atherosclerosis, progression of nonalcoholic fatty liver disease, and endothelial dysfunction. However, models of CIH have generally been implemented so as to mimic severe human OSA, with comparatively less focus on milder hypoxic regimens. Here we discuss CSH and CIH conceptually, the effects of these stimuli, and limitations of the available data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barnes, Mesarwi and Sanchez-Azofra.) more...