Ascorbic Acid Enhances Hypoxic Ventilatory Reactivity in Elderly Subjects

Pokorski, Mieczysław; Marczak, Magdalena

doi:10.1177/147323000303100514

Cited by 14 publications

(10 citation statements)

References 25 publications

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“…These findings imply an active role of the ascorbate moiety of AP in shaping the hypoxic responsiveness. The findings also conform to a human study in which the enhancement of hypoxic response to progressive hypoxia was noted in a population of elderly women after a period of supplementation with ascorbic acid [18].…”

Section: Discussionsupporting

confidence: 69%

Ascorbyl Palmitate Augments Hypoxic Respiratory Response in the Cat

2004

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The redox signaling is germane for the hypoxia-sensing mechanisms at the carotid body. This raises the strong possibility that agents possess reducing and antioxidant attributes, such as ascorbate, could influence the hypoxic respiratory response. However, water solubility of ascorbate makes its effectiveness at membrane-associated target sites dubious. In this study, we sought to determine the effect of ascorbyl-6-palmitate (AP), a lipid-soluble derivative of ascorbate which penetrates biomembranes, on hypoxic respiration in the anesthetized, paralyzed and ventilated cat. AP was given by gavage: 600 mg/kg daily for 6 days before the beginning of the acute experiment. Respiration was then assessed from the phrenic electroneurogram, from which peak phrenic amplitude, a surrogate of tidal component, respiratory frequency, and their product, the minute phrenic output, were quantified. The response to normocapnic hypoxia, 7% O₂ in N₂, in the AP-treated cats was compared with that in controls. We found that AP augmented hypoxic respiration, delayed the appearance of hypoxic depression and decreased it, although the stimulatory/depressant character was preserved. The results suggest that the ascorbate moiety of AP interacts with the hypoxia-sensing mechanisms. Ascorbate may affect hypoxic respiration at multiple stages of chemotransduction pathways, which are subject to continuing uncertainties. The study highlights the augmentative effect of AP, a redox modulator, on hypoxic respiration, which may have a therapeutic potential.

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Section: Discussionsupporting

confidence: 69%

Ascorbyl Palmitate Augments Hypoxic Respiratory Response in the Cat

2004

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“…Putting our present and previous findings together, it seems that in resting conditions, in the absence of inhibiting factors, Aox may not alter carotid body output but may increase it when such factors are present. This could be important in elderly people (> 70 years): they have been reported to possess a considerably lower O 2 sensitivity than healthy young adults (Kronenberg & Drage, 1973; Peterson et al 1981), while in women 60–80 years of age ascorbic acid supplementation appeared to increase their hypoxic response (Pokorski & Marczak, 2003). The ability of antioxidants to alter the hypoxic response may vary between different reducing agents.…”

Section: Discussionmentioning

confidence: 99%

“…In older women with an age-related reduction of hypoxic sensitivity, ascorbic acid supplementation appeared to increase their hypoxic response (Pokorski & Marczak, 2003). Recently, we showed that an antioxidant mixture, consisting of oral α-tocopherol and intravenous ascorbic acid was able to reverse the reduction of the hypoxic response in humans by subanaesthetic concentrations of inhalational anaesthetics (Teppema et al 2002(Teppema et al , 2005.…”

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confidence: 98%

“…Recently, Hildebrandt et al (2002) have shown that after a 5‐day oral application, N ‐acetylcysteine increased the hypoxic response in young adults indicating a possible specific involvement of gluthathione in oxygen sensing. In older women with an age‐related reduction of hypoxic sensitivity, ascorbic acid supplementation appeared to increase their hypoxic response (Pokorski & Marczak, 2003). Recently, we showed that an antioxidant mixture, consisting of oral α‐tocopherol and intravenous ascorbic acid was able to reverse the reduction of the hypoxic response in humans by subanaesthetic concentrations of inhalational anaesthetics (Teppema et al 2002, 2005).…”

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confidence: 99%

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Antioxidants reverse depression of the hypoxic ventilatory response by acetazolamide in man

Teppema¹,

Bijl²,

Romberg³

et al. 2006

The Journal of Physiology

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The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo-controlled double-blind study we measured the effect of an intravenous dose (4 mg kg −1 ) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83-85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid I.V. and 200 mg α-tocopherol P.O.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O 2 -CO 2 interaction, i.e. the increase in O 2 sensitivity with rising P CO 2 . Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo-and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O 2 -CO 2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen-sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude.

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“…It does not appear, however, that in healthy younger adults the HVR is improved via antioxidants alone but rather in a depressed state (45). In elderly women, however, vitamin C was shown to enhance the HVR (36). It would therefore seem plausible that COPD patients may improve their HVR following an antioxidant intervention, secondary to increased diseaserelated ROS.…”

mentioning

confidence: 95%

Cerebrovascular and ventilatory responses to acute isocapnic hypoxia in healthy aging and lung disease: effect of vitamin C

Hartmann

Waltz

Kissel

et al. 2015

Journal of Applied Physiology

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Acute hypoxia increases cerebral blood flow (CBF) and ventilation (V̇e). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (V̄p; index of CBF), and V̇e during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. V̄p and V̇e sensitivity to hypoxia was reduced in Older by ∼60% (P < 0.02). COPD patients exhibited similar V̄p and V̇e responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic V̇e response but selectively decreased the V̄p sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia.

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Ascorbic Acid Enhances Hypoxic Ventilatory Reactivity in Elderly Subjects

Cited by 14 publications

References 25 publications

Ascorbyl Palmitate Augments Hypoxic Respiratory Response in the Cat

Ascorbyl Palmitate Augments Hypoxic Respiratory Response in the Cat

Antioxidants reverse depression of the hypoxic ventilatory response by acetazolamide in man

Cerebrovascular and ventilatory responses to acute isocapnic hypoxia in healthy aging and lung disease: effect of vitamin C

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