scholarly journals Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1 

2002 ◽  
Vol 99 (2) ◽  
pp. 821-826 ◽  
Author(s):  
D. D. Kline ◽  
Y.-J. Peng ◽  
D. J. Manalo ◽  
G. L. Semenza ◽  
N. R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Chronic Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Body Function ◽  
Ventilatory Responses ◽  
Hypoxia Inducible Factor 1

scholarly journals 55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF-1

2012 ◽  
Vol 113 (9) ◽  
pp. 1343-1352 ◽  
Author(s):  
Larissa A. Shimoda
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Arterial ◽  
Expression And Activity

When exposed to chronic hypoxia (CH), the pulmonary circulation responds with enhanced contraction and vascular remodeling, resulting in elevated pulmonary arterial pressures. Our work has identified CH-induced alterations in the expression and activity of several ion channels and transporters in pulmonary vascular smooth muscle that contribute to the development of hypoxic pulmonary hypertension and uncovered a critical role for the transcription factor hypoxia-inducible factor-1 (HIF-1) in mediating these responses. Current work is focused on the regulation of HIF in the chronically hypoxic lung and evaluation of the potential for pharmacological inhibitors of HIF to prevent, reverse, or slow the progression of pulmonary hypertension.

scholarly journals Intermittent hypoxia enhances the expression of HIF1A by increasing the quantity and catalytic activity of KDM4A-C and demethylating H3K9me3 at the HIF1A locus

2021 ◽  
Author(s):  
Chloe-Anne Martinez ◽  
Neha Bal ◽  
Peter A Cistulli ◽  
Kristina M Cook
Keyword(s):  
Intermittent Hypoxia ◽  
Target Genes ◽  
Chronic Hypoxia ◽  
Oxygen Sensing ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Sensing Systems ◽  
Cellular Oxygen ◽  
Fine Tune

Cellular oxygen-sensing pathways are primarily regulated by hypoxia inducible factor-1 (HIF-1) in chronic hypoxia and are well studied. Intermittent hypoxia also occurs in many pathological conditions, yet little is known about its biological effects. In this study, we investigated how two proposed cellular oxygen sensing systems, HIF-1 and KDM4A-C, respond to cells exposed to intermittent hypoxia and compared to chronic hypoxia. We found that intermittent hypoxia increases HIF-1 activity through a pathway distinct from chronic hypoxia, involving the KDM4A, -B and -C histone lysine demethylases. Intermittent hypoxia increases the quantity and activity of KDM4A-C resulting in a decrease in H3K9 methylation. This contrasts with chronic hypoxia, which decreases KDM4A-C activity, leading to hypermethylation of H3K9. Demethylation of histones bound to the HIF1A gene in intermittent hypoxia increases HIF1A mRNA expression, which has the downstream effect of increasing overall HIF-1 activity and expression of HIF target genes. This study highlights how multiple oxygen-sensing pathways can interact to regulate and fine tune the cellular hypoxic response depending on the period and length of hypoxia.

scholarly journals Carotid body function and ventilatory responses in intermittent hypoxia. evidence for anomalous brainstem integration of arterial chemoreceptor input

2011 ◽  
Vol 226 (8) ◽  
pp. 1961-1969 ◽  
Author(s):  
M.C. Gonzalez-Martín ◽  
M.V. Vega-Agapito ◽  
S.V. Conde ◽  
J. Castañeda ◽  
R. Bustamante ◽  
...  
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Body Function ◽  
Ventilatory Responses ◽  
Arterial Chemoreceptor

scholarly journals Ventilatory responses and carotid body function in adult rats perinatally exposed to hyperoxia

2003 ◽  
Vol 554 (1) ◽  
pp. 126-144 ◽  
Author(s):  
J. Prieto-Lloret ◽  
A. I. Caceres ◽  
A. Obeso ◽  
A. Rocher ◽  
R. Rigual ◽  
...  
Keyword(s):  
Carotid Body ◽  
Adult Rats ◽  
Body Function ◽  
Ventilatory Responses

Partial HIF-1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia

2001 ◽  
Vol 281 (1) ◽  
pp. L202-L208 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Dominador J. Manalo ◽  
James S. K. Sham ◽  
Gregg L. Semenza ◽  
J. T. Sylvester
Keyword(s):  
Right Ventricular ◽  
Current Density ◽  
Chronic Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Whole Cell Patch Clamp ◽  
Electrophysiological Responses ◽  
Right Ventricular Wall ◽  
Pulmonary Arterial ◽  
Partial Deficiency

Chronic hypoxia depolarizes and reduces K+ current in pulmonary arterial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1a locus encoding HIF-1α [ Hif1a(+/−)] and from their wild-type [ Hif1a(+/+)] littermates after 3 wk in air or 10% O2. Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K+ current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1a(+/−) mice. Hypoxia increased PASMC capacitance in Hif1a(+/+) mice but not in Hif1a(+/−) mice. Chronic hypoxia depolarized and reduced K+ current density in PASMCs from Hif1a(+/+) mice. In PASMCs from hypoxic Hif1a(+/−) mice, no reduction in K+ current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1α is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy.

Carotid body excision significantly changes ventilatory control in awake rats

1988 ◽  
Vol 64 (2) ◽  
pp. 666-671 ◽  
Author(s):  
E. B. Olson ◽  
E. H. Vidruk ◽  
J. A. Dempsey
Keyword(s):  
Carotid Body ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Respiratory Acidosis ◽  
Co2 Production ◽  
Sham Operation ◽  
Ventilatory Responses ◽  
Carotid Body Chemoreceptors ◽  
Arterial Po2 ◽  
Intact Rats

We determined the effects of carotid body excision (CBX) on eupneic ventilation and the ventilatory responses to acute hypoxia, hyperoxia, and chronic hypoxia in unanesthetized rats. Arterial PCO2 (PaCO2) and calculated minute alveolar ventilation to minute metabolic CO2 production (VA/VCO2) ratio were used to determine the ventilatory responses. The effects of CBX and sham operation were compared with intact controls (PaCO2 = 40.0 +/- 0.1 Torr, mean +/- 95% confidence limits, and VA/VCO2 = 21.6 +/- 0.1). CBX rats showed 1) chronic hypoventilation with respiratory acidosis, which was maintained for at least 75 days after surgery (PaCO2 = 48.4 +/- 1.1 Torr and VA/VCO2 = 17.9 +/- 0.4), 2) hyperventilation in response to acute hyperoxia vs. hypoventilation in intact rats, 3) an attenuated increase in VA/VCO2 in acute hypoxemia (arterial PO2 approximately equal to 49 Torr), which was 31% of the 8.7 +/- 0.3 increase in VA/VCO2 observed in control rats, 4) no ventilatory acclimatization between 1 and 24 h hypoxia, whereas intact rats had a further 7.5 +/- 1.5 increase in VA/VCO2, 5) a decreased PaCO2 upon acute restoration of normoxia after 24 h hypoxia in contrast to an increased PaCO2 in controls. We conclude that in rats carotid body chemoreceptors are essential to maintain normal eupneic ventilation and to the process of ventilatory acclimatization to chronic hypoxia.

Intermittent hypoxia: cell to system

2001 ◽  
Vol 281 (3) ◽  
pp. L524-L528 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
R. Douglas Fields ◽  
Tracy Baker ◽  
Eugene C. Fletcher
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Chronic Intermittent Hypoxia ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Arterial Blood ◽  
Long Term Facilitation

This symposium was organized to present research dealing with the effects of intermittent hypoxia on cardiorespiratory systems and cellular mechanisms. The pattern of neural impulse activity has been shown to be critical in the induction of genes in neuronal cells and involves distinct signaling pathways. Mechanisms associated with different patterns of intermittent hypoxia might share similar mechanisms. Chronic intermittent hypoxia selectively augments carotid body sensitivity to hypoxia and causes long-lasting activation of sensory discharge. Intermittent hypoxia also activates hypoxia-inducible factor-1. Reactive oxygen species are critical in altering carotid body function and hypoxia-inducible factor-1 activation caused by intermittent hypoxia. Blockade of serotonin function in the spinal cord prevents long-term facilitation in respiratory motor output elicited by episodic hypoxia and requires de novo protein synthesis. Chronic intermittent hypoxia leads to sustained elevation in arterial blood pressure and is associated with upregulation of catecholaminergic and renin-angiotensin systems and downregulation of nitric oxide synthases.

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