Do genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to regulation of breathing?

Forster, H. V.; Dwinell, Melinda R.; Hodges, Matthew R.; Brozoski, Daniel; Hogan, Genevieve

doi:10.1016/s1569-9048(03)00042-9

Cited by 16 publications

(22 citation statements)

References 20 publications

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“…BN is the only strain in our study previously evaluated by others investigating strain-genetic effects on ventilatory control (13,20,37,38 no strain effects on resting minute ventilation. However, BN and Zucker rats utilized a more rapid, shallow breathing pattern relative to the other strains.…”

Section: Discussionmentioning

confidence: 94%

“…Hodges et al (20) reported that, although BN rats responded to hypoxia with less change in minute ventilation than other strains, hypoxic arterial PCO 2 (Pa CO 2 ; and therefore magnitude of hyperventilation) was similar to other strains. Although not directly measured, these data suggest BN rats experience greater hypoxia-induced hypometabolism, an effect that may be associated with genetic differences on chromosomes 9 and 18 (13). Thus it may be that the unique ventilatory response of BN rats reflects differences in the genetic determinants of metabolic regulation vs. ventilatory control per se.…”

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confidence: 80%

“…Because rats are commonly used to investigate fundamental aspects of breathing, an understanding of the genetic determinants of ventilatory control in this species is essential. Furthermore, understanding of the range of genetic variation in respiratory control may have important clinical implications in a genetically diverse population, such as humans.Differences in ventilation among inbred and outbred rat strains have been documented during eupnea (quiet breathing), hypoxia, hypercapnia, and exercise (13,20,37), and some of these changes have been associated with genotypic differences, localized to specific chromosomes (13). For example, in Brown Norway (BN) rats the frequency response to hypoxia is small compared with some other strains (20, 37).…”

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confidence: 99%

“…Differences in ventilation among inbred and outbred rat strains have been documented during eupnea (quiet breathing), hypoxia, hypercapnia, and exercise (13,20,37), and some of these changes have been associated with genotypic differences, localized to specific chromosomes (13). For example, in Brown Norway (BN) rats the frequency response to hypoxia is small compared with some other strains (20, 37).…”

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confidence: 99%

“…17) influence the neural control of breathing. Genetic influences on respiratory control have been described in rats (13,15,20,37), mice (40), and humans (42). Because rats are commonly used to investigate fundamental aspects of breathing, an understanding of the genetic determinants of ventilatory control in this species is essential.…”

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confidence: 99%

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Differences in time-dependent hypoxic phrenic responses among inbred rat strains

Golder¹,

Zabka²,

Bavis³

et al. 2005

Journal of Applied Physiology

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. Differences in time-dependent hypoxic phrenic responses among inbred rat strains. J Appl Physiol 98: 838 -844, 2005. First published November 5, 2004; doi:10.1152 doi:10. /japplphysiol.00984.2004 responses differ between rodent strains, suggesting a genetic contribution to interindividual variability. However, hypoxic ventilatory responses consist of multiple time-dependent mechanisms that can be observed in different respiratory motor outputs. We hypothesized that strain differences would exist in discrete time-dependent mechanisms of the hypoxic response and, furthermore, that there may be differences between hypoglossal and phrenic nerve responses to hypoxia. Hypoglossal and phrenic nerve responses were assessed during and after a 5-min hypoxic episode in anesthetized, vagotomized, and ventilated rats from four inbred strains: Brown Norway (BN), Fischer 344 (FS), Lewis (LW), and Piebald-viral-Glaxo (PVG). During baseline, burst frequency was higher in PVG than LW rats (P Ͻ 0.05), phrenic burst amplitude was higher in PVG vs. other strains (P Ͻ 0.05), and hypoglossal burst amplitude was higher in PVG and BN vs. FS and LW (P Ͻ 0.05). During hypoxia, burst frequency did not change in BN or LW rats, but it increased in PVG and FS rats. The phrenic amplitude response was smallest in PVG vs. other strains (P Ͻ 0.05), and the hypoglossal response was similar among strains. Short-term potentiation posthypoxia was slowest in FS and fastest in LW rats (P Ͻ 0.05). Posthypoxia frequency decline was absent in PVG, but it was observed in all other strains. Augmented breaths were observed during hypoxia in FS rats only. Thus genetic differences exist in the time domains of the hypoxic response, and these are differentially expressed in hypoglossal and phrenic nerves. Furthermore, genetic diversity observed in hypoxic ventilatory responses in unanesthetized rats may arise from multiple neural mechanisms. hypoxia; breathing; hypoglossal; genetic BOTH EXPERIENCE (i.e., plasticity; reviewed in Ref. 29) and genetics (reviewed in Ref. 17) influence the neural control of breathing. Genetic influences on respiratory control have been described in rats (13,15,20,37), mice (40), and humans (42). Because rats are commonly used to investigate fundamental aspects of breathing, an understanding of the genetic determinants of ventilatory control in this species is essential. Furthermore, understanding of the range of genetic variation in respiratory control may have important clinical implications in a genetically diverse population, such as humans.Differences in ventilation among inbred and outbred rat strains have been documented during eupnea (quiet breathing), hypoxia, hypercapnia, and exercise (13,20,37), and some of these changes have been associated with genotypic differences, localized to specific chromosomes (13). For example, in Brown Norway (BN) rats the frequency response to hypoxia is small compared with some other strains (20, 37). Hodges et al. (20) reported that, although BN rats responded to hypoxia with less change...

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 80%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Differences in time-dependent hypoxic phrenic responses among inbred rat strains

Golder¹,

Zabka²,

Bavis³

et al. 2005

Journal of Applied Physiology

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Neuroanatomic deficits in congenital central hypoventilation syndrome

Kumar

Macey

Woo

et al. 2005

J of Comparative Neurology

100

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Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High-resolution T1, proton density, and T2-weighted brain images were collected from 12 patients and 28 age- and gender-matched controls. Voxel-by-voxel T2 maps were generated from the proton density and T2-weighted images and evaluated by voxel-based-relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right-sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid-hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation.

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Systemic Oxygen Transport with Rest, Exercise, and Hypoxia: A Comparison of Humans, Rats, and Mice

González

Kuwahira

2018

Comprehensive Physiology

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The objective of this article is to compare and contrast the known characteristics of the systemic O transport of humans, rats, and mice at rest and during exercise in normoxia and hypoxia. This analysis should help understand when rodent O transport findings can-and cannot-be applied to human responses to similar conditions. The O -transport system was analyzed as composed of four linked conductances: ventilation, alveolo-capillary diffusion, circulatory convection, and tissue capillary-cell diffusion. While the mechanisms of O transport are similar in the three species, the quantitative differences are naturally large. There are abundant data on total O consumption and on ventilatory and pulmonary diffusive conductances under resting conditions in the three species; however, there is much less available information on pulmonary gas exchange, circulatory O convection, and tissue O diffusion in mice. The scarcity of data largely derives from the difficulty of obtaining blood samples in these small animals and highlights the need for additional research in this area. In spite of the large quantitative differences in absolute and mass-specific O flux, available evidence indicates that resting alveolar and arterial and venous blood PO values under normoxia are similar in the three species. Additionally, at least in rats, alveolar and arterial blood PO under hypoxia and exercise remain closer to the resting values than those observed in humans. This is achieved by a greater ventilatory response, coupled with a closer value of arterial to alveolar PO , suggesting a greater efficacy of gas exchange in the rats. © 2018 American Physiological Society. Compr Physiol 8:1537-1573, 2018.

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Do genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to regulation of breathing?

Cited by 16 publications

References 20 publications

Differences in time-dependent hypoxic phrenic responses among inbred rat strains

Differences in time-dependent hypoxic phrenic responses among inbred rat strains

Neuroanatomic deficits in congenital central hypoventilation syndrome

Systemic Oxygen Transport with Rest, Exercise, and Hypoxia: A Comparison of Humans, Rats, and Mice

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