Long-term ventilatory adaptation and ventilatory response to hypoxia in plateau pika (<i>Ochotona curzoniae</i>): role of nNOS and dopamine

Pichon, Aurélien; Bai, Zhenzhong; Favret, Fabrice; Jin, Guoen; Shufeng, Han; Marchant, Dominique; Richalet, Jean‐Paul; Ge, Ri‐Li

doi:10.1152/ajpregu.00108.2009

Cited by 31 publications

(32 citation statements)

References 57 publications

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“…As a result, the ACR in acute hypoxia is unchanged and naked mole rats do not hyperventilate. Comparatively, hyperventilation in acute hypoxia, owing to increased ventilation and/or decreased metabolism, is observed in all other adult vertebrates studied [6,18], including other fossorial species, which are also typically tolerant to prolonged hypoxia [18][19][20][21]. Thus, a maintained ACR in acute hypoxia is a novel response that may represent a beneficial adaptation in naked mole rats.…”

Section: Discussionmentioning

confidence: 96%

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

et al. 2016

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ResearchCite this article: Chung D, Dzal YA, Seow A, Milsom WK, Pamenter ME. 2016 Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia. Naked mole rats are among the most hypoxia-tolerant mammals identified and live in chronic hypoxia throughout their lives. The physiological mechanisms underlying this tolerance, however, are poorly understood. Most vertebrates hyperventilate in acute hypoxia and exhibit an enhanced hyperventilation following acclimatization to chronic sustained hypoxia (CSH). Conversely, naked mole rats do not hyperventilate in acute hypoxia and their response to CSH has not been examined. In this study, we explored mechanisms of plasticity in the control of the hypoxic ventilatory response (HVR) and hypoxic metabolic response (HMR) of freely behaving naked mole rats following 8-10 days of chronic sustained normoxia (CSN) or CSH. Specifically, we investigated the role of the major inhibitory neurotransmitter g-amino butyric acid (GABA) in mediating these responses. Our study yielded three important findings. First, naked mole rats did not exhibit ventilatory plasticity following CSH, which is unique among adult animals studied to date. Second, GABA receptor (GABAR) antagonism altered breathing patterns in CSN and CSH animals and modulated the acute HVR in CSN animals. Third, naked mole rats exhibited GABAR-dependent metabolic plasticity following longterm hypoxia, such that the basal metabolic rate was approximately 25% higher in normoxic CSH animals than CSN animals, and GABAR antagonists modulated this increase.

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Section: Discussionmentioning

confidence: 96%

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

et al. 2016

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“…Although research into the hypoxic adaptations of these rodents is at an early stage, some work regarding ventilatory control has been undertaken in pika in particular. Pika have lived at high altitude (~5000 m) for more than 30 million years and are thought to be completely acclimated to life in chronic hypoxia (314). Relative to rats, pika have lower hemoglobin concentrations, a blunted hypoxic vasoconstriction response to hypoxia, and thin-walled pulmonary arterioles to facilitate rapid gas exchange (117).…”

Section: Physiological and Molecular Responses To Prolonged Hypoxic Ementioning

confidence: 99%

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Pamenter

Powell

2016

Comprehensive Physiology

108

101

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Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields.

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“…Populations at high altitude could therefore benefit from enhancing the facilitatory mechanisms or suppressing the inhibitory ones. Some highland species or populations are characterized by a heightened acute hypoxic ventilatory response, a more effective breathing pattern, a maintained acclimatization response, and/or a prevention of hypoxic desensitization (Black and Tenney, 1980;Beall et al, 1997;Wu and Kayser, 2006;Brutsaert, 2007;Scott and Milsom, 2007;Pichon et al, 2009). The underlying chemoreceptive mechanisms are not necessarily convergent at the cellular level.…”

Section: The Nature Of Physiological Adaptation To High-altitude Hypoxiamentioning

confidence: 99%

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

Storz

Scott

Cheviron

2010

Journal of Experimental Biology

353

343

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SummaryHigh-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high-and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

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Long-term ventilatory adaptation and ventilatory response to hypoxia in plateau pika (Ochotona curzoniae): role of nNOS and dopamine

Cited by 31 publications

References 57 publications

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

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