Skip to main content
SpringerLink
Log in

Plasma adenosine concentrations during adenosine-induced respiratory stimulation in man

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Intravenous infusion of the nucleoside adenosine stimulates respiration, probably at least partly by an action in the carotid bodies, and also potentiates the ventilatory response to hypoxia, suggesting that it might be involved in the control of breathing.

Whether the effects of adenosine occur at concentrations likely to be achieved in vivo is unknown and was investigated in 7 patients with arterial catheters inserted for diagnostic purposes.

During intravenous infusion of adenosine (Maximum dose per min: mean 130 μg kg−1) mean minute ventilation increased from 5.5 to 10.9 l min−1 while mean plasma adenosine concentration in the aortic arch increased from 0.07 to 1.2 μM. In 3 patients ventilation first increased without a detectable increase in aortic adenosine concentration, suggesting a possible intra-pulmonary effect of adenosine, although increased concentrations were apparent at higher doses.

Micromolar concentrations of adenosine are probably achieved in vivo in tissues during hypoxia. The present results show that at such concentrations adenosine stimulates respiration and are consistent with the suggestion that adenosine release may mediate or modulate the ventilatory response to hypoxia. A possible intra-pulmonary effect of adenosine merits further study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anonymous (1985) A denosine revisited [Editorial]. Lancet II: 927–928

  • Berne RM, Rubio R, Curnish RR (1974) Release of adenosine from ischemic brain: effect on cerebral vascular resistance and incorporation into cerebral adenine nucleotides. Circ Res 35: 262–271

    Google Scholar 

  • Biaggioni I, Onrot J, Hollister AS, Robertson D (1986) Humoral and hemodynamic effects of adenosine infusion in man. Life Sci 39: 2229–2236

    Google Scholar 

  • Biaggioni I, Olafsson B, Robertson RM, Hollister AS, Robertson D (1987) Cardiovascular and respiratory effects of adenosine in conscious man. Evidence for chemoreceptor activation. Circ Res 61: 779–786

    Google Scholar 

  • Buss DC, Routledge PA, Watt AH (1986) Respiratory effects of intravenous adenosine in anaesthetised rabbits before and after carotid nerve section [Abstract]. Br J Pharmacol 88: 413P

  • Catravas JD (1984) Removal of adenosine from the rabbit pulmonary circulation, in vivo and in vitro. Circ Res 54: 603–611

    Google Scholar 

  • Cherniack NS, Runold M, Prabhakar NR, Mittra J (1987) Effect of adenosine on vagal sensory pulmonary afferents. Fed Proc 46: 825 [Abstract]

    Google Scholar 

  • Cheung W-T, Shi MM, Young JD, Lee CM (1987) Inhibition of radioligand binding to A1 adenosine receptors by Bay K8644 and nifedipine. Biochem Pharmacol 36: 2183–2186

    Google Scholar 

  • Conradson T-BG, Clarke B, Dixon CMS, Dalton N, Barnes PJ (1987) Effects of adenosine on autonomic control of heart rate in man. Acta Physiol Scand 131: 525–531

    Google Scholar 

  • Cunningham DJC, Gardner WN (1972) The relation between tidal volume and inspiratory and expiratory times during steady-state CO2 inhalation in man. J Physiol 227: 50P-51P

    Google Scholar 

  • Daly JW (1983) Role of ATP and adenosine receptors in physiologic processes: summary and prospectus. In: Daly JW, Kuroda Y, Phillis JW, Shimizu H, Ui M (eds) Physiology and pharmacology of adenosine derivatives. Raven Press, New York, pp 275–290

    Google Scholar 

  • Fuller RW, Maxwell DL, Conradson T-BG, Dixon CMS, Barnes PJ (1987) Circulatory and respiratory effects of infused adenosine in conscious man. Br J Clin Pharmacol 24: 309–317

    Google Scholar 

  • Kattwinkel J, Darnall RA (1982) A denosine: a possible mediator of neonatal apnea. Ped Res 16: 352A [Abstract]

  • Gamble JAS, Dundee JW, Assaf RAE (1975) Plasma diazepam levels after single dose oral and intramuscular administration. Anaesthesia 30: 164–169

    Google Scholar 

  • Griffiths TL, Warren SJ, Chant ADB, Holgate ST (1990) Ventilatory effects of adenosine infusion in patients after bilateral carotid endarterectomy. Clin Sci 78: 25–31

    Google Scholar 

  • Hammond JR, Williams EF, Clanachan AS (1985) Affinity of calcium channel inhibitors, benzodiazepines, and other vasoactive compounds for the nucleoside transport system. Can J Physiol Pharmacol 63: 1302–1307

    Google Scholar 

  • Hedner T, Hedner J, Wessberg P, Jonason J (1982) Regulation of breathing in the rat: indications for a role of central adenosine mechanisms. Neurosci Lett 33: 147–151

    Google Scholar 

  • Hellewell PG, Pearson JD (1983) Metabolism of circulating adenosine by the porcine isolated perfused lung. Circ Res 53: 1–7

    Google Scholar 

  • Hugelin A (1986) Forebrain and midbrain influence on respiration. In: Fishman AP, Cherniack NS, Widdicombe JG, Geiger SR (eds); Handbook of Physiology, Section 3: The respiratory system. Bethesda, Maryland, American Physiology Society, pp 69–91

    Google Scholar 

  • Ikram H, Rubin AP, Jewkes RF (1973) Effect of diazepam on myocardial blood flow of patients with and without coronary artery disease. Br Heart J 35: 626–630

    Google Scholar 

  • Jennett S, Russell T, Warnock KA (1974) The duration of inspiration during changing states of ventilation in man. J Physiol 238: 54P-55P

    Google Scholar 

  • Khym JX (1975) An analytical system for rapid separation of tissue nucleotides at low pressures on conventional anion exchanges. Clin Chem 21: 1245–1252

    Google Scholar 

  • Lugliani R, Whipp BJ, Seard C, Wasserman K (1971) Effect of bilateral carotid-body resection on ventilatory control at rest and during exercise in man. N Engl J Med 285: 1105–1111

    Google Scholar 

  • Mann JS, Holgate T, Renwick AG, Cushley MJ (1986) Airway effects of purine nucleosides and nucleotides and release with bronchial provocation in asthma. J Appl Physiol 61: 1667–1676

    Google Scholar 

  • Maxwell DL, Fuller RW, Nolop KB, Dixon CMS, Hughes JMB (1986) Effects of adenosine on ventilatory responses to hypoxia and hypercapnia in humans. J Appl Physiol 61: 1762–1766

    Google Scholar 

  • McQueen DS, Ribeiro JA (1981) Effect of adenosine on carotid chemoreceptor activity in the cat. Br J Pharmacol 74: 129–136

    Google Scholar 

  • McQueen DS, Ribeiro JA (1986) Pharmacological characterisation of the receptor involved in chemoexcitation induced by adenosine. Br J Clin Pharmacol 88: 615–620

    Google Scholar 

  • Mentzer RM, Rubio R, Berne RM (1975) Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation. Am J Physiol 229: 1625–1631

    Google Scholar 

  • Merrill G, Young M, Dorell S, Krieger L (1982) Coronary interactions between nifedipine and adenosine in the intact dog heart. Eur J Pharmacol 82: 543–550

    Google Scholar 

  • Monteiro EC, Ribeiro JA (1987) Ventilatory effects of adenosine mediated by carotid body chemoreceptors in the rat. Arch Pharmacol 335: 143–148

    Google Scholar 

  • Möser GH, Schrader J, Deussen A (1989) Turnover of adenosine in plasma of human and dog blood. Am J Physiol 256: C799-C806

    Google Scholar 

  • Newsom Davis J, Stagg D (1975) Interrelationships of the volume and time components of individual breaths in resting man. J Physiol 245: 481–498

    Google Scholar 

  • Park TS, Van Wylen DGL, Rubio R, Berne RM (1986) Increased brain interstitial fluid adenosine concentration during hypoxia in newborn piglet. J Cereb Blood Flow Metab 7: 178–183

    Google Scholar 

  • Phillis JW, Bender AS, Wu PH (1980) Benzodiazepines inhibit adenosine uptake into rat brain synaptosomes. Brain Res 195: 494–498

    Google Scholar 

  • Reid PG, Watt AH, Routledge PA, Smith AP (1987) Intravenous infusion of adenosine but not inosine stimulates respiration in man. Br J Clin Pharmacol 23: 331–338

    Google Scholar 

  • Reid PG, Fraser AG, Watt AH, Henderson AH, Routledge PA (1990) Acute haemodynamic effects of intravenous infusion of adenosine in conscious man. Eur Heart J 11: 1018–1028

    Google Scholar 

  • Rubio R, Wiedmeier VT, Berne RM (1974) Relationship between coronary flow and adenosine production and release. J Moll Cell Cardiol 6: 561–566

    Google Scholar 

  • Rubio R, Berne RM, Bockman EL, Curnish RR (1975) Relationship between adenosine concentration and oxygen supply in rat brain. Am J Physiol 228: 1896–1902

    Google Scholar 

  • Runold M, Prabhakar NR, Mittra J, Cherniak NS (1987) Adenosine stimulates respiration by acting on vagal receptors. Fed Proc 46: 825 [Abstract]

    Google Scholar 

  • Sollevi A (1986) Cardiovascular effects of adenosine in man: Possible clinical implications. Prog Neurobiol 27: 319–349

    Google Scholar 

  • Sollevi A, Lagerkranser M, Irestedt L, Gordon E, Lindqvist C (1984) Controlled hypotension with adenosine in cerebral aneurysm surgery. Anesthesiol 61: 400–405

    Google Scholar 

  • Sollevi A, Östergren J, Fagrell B, Hjemdahl P (1984) Theophylline antagonises cardiovascular responses to dipyridamole in man without affecting increases in plasma adenosine. Acta Phys Scand 121: 165–171

    Google Scholar 

  • Sorkin EM, Clissold SP, Brogden RN (1985) Nifedipine: A review. Drugs 30: 182–274

    Google Scholar 

  • Sylvén C, Jonzen B, Brandt R, Beerman B (1987) Adenosine-provoked angina pectoris-like pain — time characteristics, influence of autonomic blockade and naloxone. Eur Heart J 8: 738–743

    Google Scholar 

  • Treves S, Maltz DL, Adelstein SJ (1974) Intracardiac shunts. In: Pediatric Nuclear Medicine, James AE, Wagner HN, Cooke RE (eds), Saunders, Philadelphia, pp 231–246

    Google Scholar 

  • van Calker D, Müller M, Hamprecht B (1979) Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 33: 999–1005

    Google Scholar 

  • Watt AH, Reid PG, Stephens MR, Routledge PA (1987) Adenosine-induced respiratory stimulation depends on site of infusion. Evidence for an action on the carotid body? Br J Clin Pharmacol 23: 486–490

    Google Scholar 

  • Watt AH, Routledge PA (1985) Adenosine stimulates respiration in man. Br J Clin Pharmacol 20: 503–506

    Google Scholar 

  • Watt AH, Routledge PA (1986) Adenosine: an importance beyond ATP. Br Med J 293: 1455–1456

    Google Scholar 

  • Wojcik WJ, Neff NH (1982) Adenosine measurement by a rapid HPLC-fluorometric method: induced changes of adenosine content in regions of rat brain. J Neurochem 39: 280–282

    Google Scholar 

  • Zimmerman PV, Connellman SJ, Middleton HC, Tabona MV, Goldman MD, Pride N (1983) Postural changes in rib cage and abdominal volume-motion coefficients and their effect on the calibration of a respiratory inductance plethysmograph. Am Rev Resp Dis 127: 209–214

    Google Scholar 

Download references

Author information

Author notes

  1. P. G. Reid

    Present address: Cardiology Department, Royal Victoria Infirmary, NE1 4LP, Newcastle upon Tyne

  2. A. H. Watt

    Present address: Medicines Assessment Research Unit, University of Aberdeen, Medical School, Foresterhill, AB9 2ZD, Aberdeen, U.K.

Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, CF4 4XN, Cardiff

    P. G. Reid, A. H. Watt & P. A. Routledge

  2. Department of Cardiology, University of Wales College of Medicine, Heath Park, CF4 4XN, Cardiff

    W. J. Penny & A. C. Newby

  3. Department of Respiratory Medicine, Llandough Hospital, CF6 1XX, Penarth, South Glamorgan, UK

    A. P. Smith

Authors
  1. P. G. Reid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. H. Watt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. J. Penny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. C. Newby
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. P. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. A. Routledge
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reid, P.G., Watt, A.H., Penny, W.J. et al. Plasma adenosine concentrations during adenosine-induced respiratory stimulation in man. Eur J Clin Pharmacol 40, 175–180 (1991). https://doi.org/10.1007/BF00280073

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00280073

Key words

Search

Navigation