Plasma Adenosine during Investigation of Hypoxic Ventilatory Response

 

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Adenosine, an endogenous nucleoside, is released by hypoxic tissue, causes vasodilation, and influences ventilation. Its effects are mediated by P1-purinoceptors. We examined to what extent the plasma adenosine concentration in the peripheral venous blood correlates with hypoxic ventilatory response (HVR) and ventilatory drive P0.1 to find out whether endogenously formed adenosine has an influence on the individual ventilatory drive under hypoxic conditions. While investigating the HVR of 14 healthy subjects, the ventilatory drive P0.1 was measured with the shutter of a spirometer. Determination of the ventilatory drive P0.1(RA) started under room air conditions (21% O₂) and then inspiratory gas was changed to a hypoxic mixture of 10% O₂ in N₂ to determine P0.1(Hyp). At the time of the P0.1 measurements, two blood samples were taken to determine the adenosine concentrations. After removal of cellular components and proteins, samples were analyzed by high-pressure liquid chromatography (HPLC). Both adenosine concentrations in plasma under room air (r = 0.59, p < 0.05) and adenosine concentrations under hypoxia (r = 0.75, p < 0.01) correlated significantly with the ventilatory drive P0.1. In addition, plasma adenosine concentrations during hypoxic conditions showed a significant correlation with HVR on the 0.01 level (r = 0.71, p < 0.01). The results indicate a possible role of endogenous adenosine in the regulation of breathing in humans. We assume that endogenous adenosine influences the HVR and the ventilatory drive, probably by modulating the carotid body chemoreceptor response to hypoxia.

REFERENCES

• 1 Möser G H, Schrader J, Deussen A. Turnover of adenosine in plasma of human and dog blood.  Am J Physiol. 1989;  256(4 Pt 1) C799-C806
  PubMedGoogle Scholar
• 2 Kobayashi S, Zimmermann H, Millhorn D E. Chronic hypoxia enhances adenosine release in rat PC12 cells by altering adenosine metabolism and membrane transport.  J Neurochem. 2000;  74 621-632
  CrossrefPubMedGoogle Scholar
• 3 Huszár É, Barát E, Kollai M. Isocratic high-performance liquid chromatographic determination of plasma adenosine.  Chromatographia. 1996;  42 318-322
  PubMedGoogle Scholar
• 4 Jonzon B. Adenosine Mechanisms in the Central Nervous System [doctoral thesis]. Stockholm, Sweden; Karolinska Institute 1984: 10-21
  Google Scholar
• 5 Bryan P T, Marshall J M. Adenosine receptor subtypes and vasodilatation in rat skeletal muscle during systemic hypoxia: a role for A1 receptors.  J Physiol. 1999;  514 151-162
  CrossrefPubMedGoogle Scholar
• 6 Coney A M, Marshall J M. Role of adenosine and its receptors in the vasodilatation induced in the cerebral cortex of the rat by systemic hypoxia.  J Physiol. 1998;  509 507-518
  CrossrefPubMedGoogle Scholar
• 7 Georgopoulos D, Holthby S G, Berezanski D, Anthonisen N R. Aminophylline effects on ventilatory response to hypoxia and hyperoxia in normal adults.  J Appl Physiol. 1989;  67 1150-1156
  PubMedGoogle Scholar
• 8 Gleeson K, Zwillich C W. Adenosine infusion and periodic breathing during sleep.  J Appl Physiol. 1992;  72 1004-1009
  PubMedGoogle Scholar
• 9 Reid P G, Watt A H, Penny W J, Newby A C, Smith A P, Routledge P A. Plasma adenosine concentrations during adenosine-induced respiratory stimulation in man.  Eur J Clin Pharmacol. 1991;  40 175-180
  PubMedGoogle Scholar
• 10 Smits P, Schouten J, Thien T H. Respiratory stimulant effects of adenosine in man after caffeine and enprofylline.  Br J Clin Pharmacol. 1987;  24 816-819
  PubMedGoogle Scholar
• 11 Saito H, Nishimura M, Shinano H et al.. Plasma concentration of adenosine during normoxia and moderate hypoxia in humans.  Am J Respir Crit Care Med. 1999;  159 1014-1018
  PubMedGoogle Scholar
• 12 Easton P A, Slykerman L J, Anthonisen N R. Ventilatory response to sustained hypoxia in normal adults.  J Appl Physiol. 1986;  61 906-911
  PubMedGoogle Scholar
• 13 Bärtsch P, Grünig E, Hohenhaus E, Dehnert C. Assessment of high altitude tolerance in healthy individuals.  High Alt Med Biol. 2001;  2 287-296
  PubMedGoogle Scholar
• 14 Hirshman C A, McCullough R E, Weil J V. Normal values for hypoxic and hypercapnic ventilatory drive in man.  J Appl Physiol. 1975;  38 1095-1098
  PubMedGoogle Scholar
• 15 Hohenhaus E, Paul A, McCullough R E, Kücherer H, Bärtsch P. Ventilatory and pulmonary vascular response to hypoxia and susceptibility to high altitude pulmonary oedema.  Eur Respir J. 1995;  8 1825-1833
  CrossrefPubMedGoogle Scholar
• 16 van Klaveren R J, Demedts M. Determinants of the hypercapnic and hypoxic response in normal man.  Respir Physiol. 1998;  113 157-165
  CrossrefPubMedGoogle Scholar
• 17 Matsuzawa Y, Fujimoto K, Kobayashi T et al.. Blunted hypoxic ventilatory drive in subjects susceptible to high-altitude pulmonary edema.  J Appl Physiol. 1989;  66 1152-1157
  PubMedGoogle Scholar
• 18 Milledge J S, Thomas P S, Beeley J M, English J SC. Hypoxic ventilatory response and acute mountain sickness.  Eur Respir J. 1988;  1 948-951
  PubMedGoogle Scholar
• 19 Nishimura M, Yamamoto M, Yoshioka A, Akiyama Y, Kishi F, Kawakami Y. Longitudinal analyses of respiratory chemosensitivity in normal subjects.  Am Rev Respir Dis. 1991;  143 1278-1281
  PubMedGoogle Scholar
• 20 Sahn S A, Zwillich C W, Dick N, McCullough R E, Lakshminarayan S, Weil J V. Variability of ventilatory responses to hypoxia and hypercapnia.  J Appl Physiol. 1977;  43 1019-1025
  PubMedGoogle Scholar
• 21 West J B. Rate of ventilatory acclimatization to extreme altitude.  Respir Physiol. 1988;  74 323-333
  CrossrefPubMedGoogle Scholar
• 22 Hackett P H, Roach R C, Schoene R B, Harrison G L, Mills W J. Abnormal control of ventilation in high-altitude pulmonary edema.  J Appl Physiol. 1988;  64 1268-1272
  PubMedGoogle Scholar
• 23 Insalaco G, Romano S, Salvaggio A et al.. Cardiovascular and ventilatory response to isocapnic hypoxia at sea level and at 5050 m.  J Appl Physiol. 1996;  80 1724-1730
  PubMedGoogle Scholar
• 24 Sugimori K, Amin H M, Esposito B F, Seedat M S, Camporesi E M. Effect of slow versus fast desaturation on the ventilatory response to hypoxia.  J Med. 1996;  27 277-292
  PubMedGoogle Scholar
• 25 Milic-Emili J, Whitelaw W A, Derenne J P. New tests to assess lung function: occlusion pressure-a simple measure of the respiratory center's output.  N Engl J Med. 1975;  293 1029-1030
  PubMedGoogle Scholar
• 26 Whitelaw W A, Derenne J P, Millic-Emili J. Occlusion pressure as a measure of respiratory center output in conscious man.  Respir Physiol. 1975;  23 181-199
  CrossrefPubMedGoogle Scholar
• 27 Honda Y. Ventilatory depression during mild hypoxia in adult humans.  Jpn J Physiol. 1995;  45 947-959
  CrossrefPubMedGoogle Scholar
• 28 Moore L G, Harrison G L, McCullough R E et al.. Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness.  J Appl Physiol. 1986;  60 1407-1412
  PubMedGoogle Scholar
• 29 Sato M, Severinghaus J W, Bickler P. Time course of augmentation and depression of hypoxic ventilatory responses at altitude.  J Appl Physiol. 1994;  77 313-316
  PubMedGoogle Scholar
• 30 Maxwell D L, Fuller R W, Nolop K B, Dixon C MS, Hughes M B. Effects of adenosine on ventilatory responses to hypoxia and hypercapnia.  J Appl Physiol. 1986;  61 1762-1766
  PubMedGoogle Scholar
• 31 Parsons S T, Griffiths T L, Christie J ML, Holgate S T. Effect of theophylline and dipyridamole on the respiratory response to isocapnic hypoxia in normal subjects.  Clin Sci Lond. 1991;  80 107-112
  PubMedGoogle Scholar
• 32 Watt A H, Routledge P A. Adenosine stimulates respiration in man.  Br J Clin Pharmacol. 1985;  20 503-506
  PubMedGoogle Scholar
• 33 Johnson T S, Rock P B. Acute mountain sickness.  N Engl J Med. 1988;  319 841-845
  PubMedGoogle Scholar
• 34 Griffiths T L, Christie J ML, Parsons S T, Holgate S T. The effect of dipyridamole and theophylline on hypercapnic ventilatory responses: the role of adenosine.  Eur Respir J. 1997;  10 156-160
  CrossrefPubMedGoogle Scholar

Dirk DrummM.D. 

Innere Medizin V

Universitätskliniken des Saarlandes

66421 Homburg/Saar, Germany

Email: ddrumm@onlinehome.de