Temporal changes of plasma erythropoietin level in hypobaric hypoxic mice and the influence of an altered blood oxygen affinity.

Shimizu, Satoshi; Satoh, Susumu; Enoki, Yasunori; Ohga, Yoshimi; Oki, Izumi; Kohzuki, Hisaharu

doi:10.2170/jjphysiol.39.833

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…Preconditioning the animals with S1P for three days prior to hypoxia exposure led to increased HIF-1α level (Figure 1a) which further caused higher levels of plasma Epo (Figure 1a) [28]. The kidney is highly sensitive to oxygen levels and plays a central role in mediating the hypoxic induction of RBCs via Epo synthesis, a key step for physiological adaptation to sub-optimal oxygen [29]. Increased Epo, within 2 hours of hypobaric hypoxia exposure, triggers erythropoiesis over days, which is an adaptive response to facilitate acclimatization to high altitude [30].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Sphingosine-1-Phosphate Boosts Acclimatization in Rats Exposed to Acute Hypobaric Hypoxia: Assessment of Haematological and Metabolic Effects

et al. 2014

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BackgroundThe physiological challenges posed by hypobaric hypoxia warrant exploration of pharmacological entities to improve acclimatization to hypoxia. The present study investigates the preclinical efficacy of sphingosine-1-phosphate (S1P) to improve acclimatization to simulated hypobaric hypoxia.Experimental ApproachEfficacy of intravenously administered S1P in improving haematological and metabolic acclimatization was evaluated in rats exposed to simulated acute hypobaric hypoxia (7620m for 6 hours) following S1P pre-treatment for three days.Major FindingsAltitude exposure of the control rats caused systemic hypoxia, hypocapnia (plausible sign of hyperventilation) and respiratory alkalosis due to suboptimal renal compensation indicated by an overt alkaline pH of the mixed venous blood. This was associated with pronounced energy deficit in the hepatic tissue along with systemic oxidative stress and inflammation. S1P pre-treatment improved blood oxygen-carrying-capacity by increasing haemoglobin, haematocrit, and RBC count, probably as an outcome of hypoxia inducible factor-1α mediated erythropoiesis and renal S1P receptor 1 mediated haemoconcentation. The improved partial pressure of oxygen in the blood could further restore aerobic respiration and increase ATP content in the hepatic tissue of S1P treated animals. S1P could also protect the animals from hypoxia mediated oxidative stress and inflammation.ConclusionThe study findings highlight S1P’s merits as a preconditioning agent for improving acclimatization to acute hypobaric hypoxia exposure. The results may have long term clinical application for improving physiological acclimatization of subjects venturing into high altitude for occupational or recreational purposes.

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Section: Discussionmentioning

confidence: 99%

Exogenous Sphingosine-1-Phosphate Boosts Acclimatization in Rats Exposed to Acute Hypobaric Hypoxia: Assessment of Haematological and Metabolic Effects

et al. 2014

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“…The gp91 phoxand p47 phox -null mutant and the respective wild-type mice were maintained in hypobaric hypoxia (0.5 atm) or normobaric normoxia for 72 h. In Salt Lake City, UT (647 Torr barometric pressure), this degree of hypobaria corresponds to a dry gas inspired PO2 of 63 Torr. Similar conditions of hypobaria have been found to induce maximal EPO production in mice (44). To evaluate for increased sensitivity to hypoxia, the p47 phox -null mutant and wild-type mice were also exposed to an intermediate hypobaric (0.75 atm) stimulus corresponding to a dry gas inspired PO 2 of 94.5 Torr for 48 h.…”

Section: Animalsmentioning

confidence: 99%

Role of components of the phagocytic NADPH oxidase in oxygen sensing

Sanders

Sundar²,

et al. 2002

Journal of Applied Physiology

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It has been hypothesized that O(2) sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O(2) sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study unanesthetized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91(phox)-null mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47(phox)-null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 +/- 18.0 vs. 20.0 +/- 13.0% (n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47(phox)-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47(phox)-null mutant than in wild-type mice: 109.61 +/- 13.29 vs. 72.54 +/- 7.65 impulses/s (n = 8 and 7, respectively, P = 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was approximately 58% larger in p47(phox)-null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91(phox)- and p47(phox)-null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91(phox) component of the phagocytic NADPH oxidase does not alter the O(2)-sensing mechanism of the carotid body. However, absence of the p47(phox) component significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O(2) sensing in EPO-producing cells of the kidney appears to be independent of the gp91(phox) and p47(phox) components of the phagocytic NADPH oxidase.

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“…It has been argued that ventilation with room air may not be ideal in mice (24), based on observed high murine P 50 values (PO 2 corresponding to 50 % hemoglobin saturation) of 65 mmHg (46) or even 71 mmHg (48). However, most studies have found a P 50~ 40 mmHg for the mouse, when measured under standard conditions (pH = 7.4, PCO 2 = 40 mmHg, 37 ¡C) (25,31,35,42,47). A P 50 of ~ 40 mmHg is still rightshifted, when compared to humans (P 50 = 28 mmHg).…”

Section: Partial Pressures Of Gassesmentioning

confidence: 99%

Mechanical ventilation of mice

Schwarte

Zuurbier

İnce

2000

Basic Research in Cardiology

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Due to growing interest in murine functional genomics research, there is an increasing need for physiological stable in vivo murine models. Of special importance is support and control of ventilation by artificial respiration, which is difficult to execute as a consequence of the small size of the animal and the technically demanding breathing pattern. In addition, numerous genetically altered mice show depressed spontaneous ventilation or impaired respiratory responses. After an introduction in murine respiratory physiology we describe options for ventilatory support, its monitoring and the potential side effects. This review will provide an overview on current possibilities in the field of airway support in mouse research.

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Temporal changes of plasma erythropoietin level in hypobaric hypoxic mice and the influence of an altered blood oxygen affinity.

Cited by 7 publications

References 19 publications

Exogenous Sphingosine-1-Phosphate Boosts Acclimatization in Rats Exposed to Acute Hypobaric Hypoxia: Assessment of Haematological and Metabolic Effects

Exogenous Sphingosine-1-Phosphate Boosts Acclimatization in Rats Exposed to Acute Hypobaric Hypoxia: Assessment of Haematological and Metabolic Effects

Role of components of the phagocytic NADPH oxidase in oxygen sensing

Mechanical ventilation of mice

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