Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2016

Open Access 01-12-2016 | Research article

Lower hypoxic ventilatory response in smokers compared to non-smokers during abstinence from cigarettes

Authors: Wulf Hildebrandt, Roland Sauer, Ulrich Koehler, Peter Bärtsch, Ralf Kinscherf

Published in: BMC Pulmonary Medicine | Issue 1/2016

Login to get access

Abstract

Background

Carotid body O2-chemosensitivity determines the hypoxic ventilatory response (HVR) as part of crucial regulatory reflex within oxygen homeostasis. Nicotine has been suggested to attenuate HVR in neonates of smoking mothers. However, whether smoking affects HVR in adulthood has remained unclear and probably blurred by acute ventilatory stimulation through cigarette smoke. We hypothesized that HVR is substantially reduced in smokers when studied after an overnight abstinence from cigarettes i.e. after nicotine elimination.

Methods

We therefore determined the isocapnic HVR of 23 healthy male smokers (age 33.9 ± 2.0 years, BMI 24.2 ± 0.5 kg m−2, mean ± SEM) with a smoking history of >8 years after 12 h of abstinence and compared it to that of 23 healthy male non-smokers matched for age and BMI.

Results

Smokers and non-smokers were comparable with regard to factors known to affect isocapnic HVR such as plasma levels of glucose and thiols as well as intracellular levels of glutathione in blood mononuclear cells. As a new finding, abstinent smokers had a significantly lower isocapnic HVR (0.024 ± 0.002 vs. 0.037 ± 0.003 l min−1 %−1BMI−1, P = 0.002) compared to non-smokers. However, upon re-exposure to cigarettes the smokers’ HVR increased immediately to the non-smokers’ level.

Conclusions

This is the first report of a substantial HVR reduction in abstinent adult smokers which appears to be masked by daily smoking routine and may therefore have been previously overlooked. A low HVR may be suggested as a novel link between smoking and aggravated hypoxemia during sleep especially in relevant clinical conditions such as COPD.
Appendix
Available only for authorised users
Literature
1.
go back to reference Blain GM, Smith CA, Henderson KS, Dempsey JA. Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetised dog. J Appl Physiol. 2009;106(5):1564–73.CrossRefPubMedPubMedCentral Blain GM, Smith CA, Henderson KS, Dempsey JA. Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetised dog. J Appl Physiol. 2009;106(5):1564–73.CrossRefPubMedPubMedCentral
2.
go back to reference Moore CG, Zwillich CW, Battaglia J, Cottom EK, Weil JV. Respiratory failure associated with familial depression of ventilator responses to hypoxia and hypercarbia. N Engl J Med. 1976;295:861–5.CrossRefPubMed Moore CG, Zwillich CW, Battaglia J, Cottom EK, Weil JV. Respiratory failure associated with familial depression of ventilator responses to hypoxia and hypercarbia. N Engl J Med. 1976;295:861–5.CrossRefPubMed
4.
go back to reference Prabhakar NR, Peng YJ. Peripheral chemoreceptors in health and disease. J Appl Physiol. 2004;96:359–66.CrossRefPubMed Prabhakar NR, Peng YJ. Peripheral chemoreceptors in health and disease. J Appl Physiol. 2004;96:359–66.CrossRefPubMed
5.
go back to reference Wade JG, Larson Jr CP, Hickey RF, Ehrenfeld WK, Severinghaus JW. Effect of carotid endarterectomy on the carotid chemoreceptor and baroreceptor function in man. N Engl J Med. 1970;282:823–9.CrossRefPubMed Wade JG, Larson Jr CP, Hickey RF, Ehrenfeld WK, Severinghaus JW. Effect of carotid endarterectomy on the carotid chemoreceptor and baroreceptor function in man. N Engl J Med. 1970;282:823–9.CrossRefPubMed
6.
go back to reference Gries RE, Brooks LJ. Normal oxyhemoglobin saturation during sleep. How low does it go ? Chest. 1996;110(6):1489–92.CrossRefPubMed Gries RE, Brooks LJ. Normal oxyhemoglobin saturation during sleep. How low does it go ? Chest. 1996;110(6):1489–92.CrossRefPubMed
8.
go back to reference Weil JV, Bryne-Quinn E, Sodal EI, Friesen WD, Underhill B, Filley GF, Grover RF. Hypoxic ventilatory response in normal men. J Clin Invest. 1970;49:1061–72.CrossRefPubMedPubMedCentral Weil JV, Bryne-Quinn E, Sodal EI, Friesen WD, Underhill B, Filley GF, Grover RF. Hypoxic ventilatory response in normal men. J Clin Invest. 1970;49:1061–72.CrossRefPubMedPubMedCentral
9.
go back to reference Richalet JP, Larmignat P, Poitrine E, Letournel M, Canouï-Poitrine F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. Am J Respir Crit Care Med. 2002;185(2):192–8.CrossRef Richalet JP, Larmignat P, Poitrine E, Letournel M, Canouï-Poitrine F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. Am J Respir Crit Care Med. 2002;185(2):192–8.CrossRef
10.
go back to reference Lhuissier FJ, Brumm M, Ramier D, Richalet JP. Ventilatory and cardiac response to hypoxia at submaximal exercise are independent of altitude and exercise intensity. J Appl Physiol. 2012;112:566–70.CrossRefPubMed Lhuissier FJ, Brumm M, Ramier D, Richalet JP. Ventilatory and cardiac response to hypoxia at submaximal exercise are independent of altitude and exercise intensity. J Appl Physiol. 2012;112:566–70.CrossRefPubMed
11.
go back to reference Kara T, Narkiewicz K, Somers VK. Chemoreflexes - physiology and clinical implications. Acta Physiol Scand. 2003;177(3):377–84.CrossRefPubMed Kara T, Narkiewicz K, Somers VK. Chemoreflexes - physiology and clinical implications. Acta Physiol Scand. 2003;177(3):377–84.CrossRefPubMed
12.
go back to reference Osanai S, Akiba Y, Fujiuchi S, Nakano H, Matsumoto H, Ohsaki Y, Kikuchi K. Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients with obstructive sleep apnoea syndrom. Eur Respir J. 1999;13(2):418–23.CrossRefPubMed Osanai S, Akiba Y, Fujiuchi S, Nakano H, Matsumoto H, Ohsaki Y, Kikuchi K. Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients with obstructive sleep apnoea syndrom. Eur Respir J. 1999;13(2):418–23.CrossRefPubMed
14.
go back to reference Byrne-Quinn E, Weil JV, Sodal IE, Filley GF, Grover RF. Ventilatory control in the athlete. J Appl Physiol. 1971;30:91–8.PubMed Byrne-Quinn E, Weil JV, Sodal IE, Filley GF, Grover RF. Ventilatory control in the athlete. J Appl Physiol. 1971;30:91–8.PubMed
15.
go back to reference Kronenberg RS, Drage CW. Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men. J Clin Invest. 1973;52:1812–9.CrossRefPubMedPubMedCentral Kronenberg RS, Drage CW. Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men. J Clin Invest. 1973;52:1812–9.CrossRefPubMedPubMedCentral
17.
go back to reference Weil JV, Byrne-Quinn E, Sodal IE, Filley GF, Grover RF. Acquired attenuation of chemoreceptor function in chronically hypoxic man at altitude. J Clin Invest. 1971;50:186–95.CrossRefPubMedPubMedCentral Weil JV, Byrne-Quinn E, Sodal IE, Filley GF, Grover RF. Acquired attenuation of chemoreceptor function in chronically hypoxic man at altitude. J Clin Invest. 1971;50:186–95.CrossRefPubMedPubMedCentral
18.
go back to reference Stéphan-Blanchard E, Chardon K, Léké A, Delanaud S, Djeddi D, Libert JP, Bach V, Telliez F. In utero exposure to smoking and peripheral chemoreceptor function in preterm neonates. Pediatrics. 2010;125(3):592–9.CrossRef Stéphan-Blanchard E, Chardon K, Léké A, Delanaud S, Djeddi D, Libert JP, Bach V, Telliez F. In utero exposure to smoking and peripheral chemoreceptor function in preterm neonates. Pediatrics. 2010;125(3):592–9.CrossRef
19.
go back to reference Hafstrom O, Milerad J, Sandberg KL, Sundell HW. Cardiorespiratory effects of nicotine exposure during development. Respir Physiol Neurobiol. 2005;149:325–41.CrossRefPubMed Hafstrom O, Milerad J, Sandberg KL, Sundell HW. Cardiorespiratory effects of nicotine exposure during development. Respir Physiol Neurobiol. 2005;149:325–41.CrossRefPubMed
20.
go back to reference Huang YH, Brown AR, Cross SJ, Cruz J, Rice A, Jaiswal S, Fregosi RF. Influence of prenatal nicotine exposure on development of ventilator response to hypoxia and hypercapnia in neonatal rats. J Appl Physiol. 2010;109(1):149–58.CrossRefPubMedPubMedCentral Huang YH, Brown AR, Cross SJ, Cruz J, Rice A, Jaiswal S, Fregosi RF. Influence of prenatal nicotine exposure on development of ventilator response to hypoxia and hypercapnia in neonatal rats. J Appl Physiol. 2010;109(1):149–58.CrossRefPubMedPubMedCentral
21.
go back to reference Nelson EA, Taylor BJ. International child care practices study: infant sleep position and parental smoking. Early Hum Dev. 2001;64(1):7–20.CrossRefPubMed Nelson EA, Taylor BJ. International child care practices study: infant sleep position and parental smoking. Early Hum Dev. 2001;64(1):7–20.CrossRefPubMed
22.
go back to reference Cohen G, Roux JC, Grailhe R, Malcolm G, Changeux JP, Lagercrantz H. Perinatal exposure to nicotine causes deficits associated with a loss of nicotinic receptor function. PNAS. 2005;102(10):3817–21.CrossRefPubMedPubMedCentral Cohen G, Roux JC, Grailhe R, Malcolm G, Changeux JP, Lagercrantz H. Perinatal exposure to nicotine causes deficits associated with a loss of nicotinic receptor function. PNAS. 2005;102(10):3817–21.CrossRefPubMedPubMedCentral
23.
go back to reference Cohen G, Han ZH, Grailhe R, Gallego J, Gaultier C, Changeux JP, Lagercrantz H. β2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: a --receptor basis for sleep disordered breathing after nicotine exposure. PNAS. 2002;99(20):13272–7.CrossRefPubMedPubMedCentral Cohen G, Han ZH, Grailhe R, Gallego J, Gaultier C, Changeux JP, Lagercrantz H. β2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: a --receptor basis for sleep disordered breathing after nicotine exposure. PNAS. 2002;99(20):13272–7.CrossRefPubMedPubMedCentral
24.
go back to reference Sovik S, Lossiu K, Walloe L. Heart rate response to transient chemoreceptor stimulation in term infants is modified by exposure to maternal smoking. Pediatr Res. 2001;49:558–65.CrossRefPubMed Sovik S, Lossiu K, Walloe L. Heart rate response to transient chemoreceptor stimulation in term infants is modified by exposure to maternal smoking. Pediatr Res. 2001;49:558–65.CrossRefPubMed
25.
go back to reference Ueda Y, Stick SM, Hall G, Sly PD. Control of breathing in infants born to smoking mothers. J Pediatr. 1999;135:226–32.CrossRefPubMed Ueda Y, Stick SM, Hall G, Sly PD. Control of breathing in infants born to smoking mothers. J Pediatr. 1999;135:226–32.CrossRefPubMed
26.
go back to reference Kawakami Y, Yamamoto H, Yoshikawa T, Shida A. Respiratory chemosensitivity in smokers - studies on monozygotic twin. Am Rev Respir Dis. 1982;126:986–90.PubMed Kawakami Y, Yamamoto H, Yoshikawa T, Shida A. Respiratory chemosensitivity in smokers - studies on monozygotic twin. Am Rev Respir Dis. 1982;126:986–90.PubMed
27.
go back to reference Argacha JF, Xhaet O, Gujic M, Adamopoulos D, Beloka S, Dreyfuss C, Degaute JP, van de Borne P. Nicotine increases chemoreflex sensitivity to hypoxia in non-smokers. J Hypertension. 2008;26(2):284–94.CrossRef Argacha JF, Xhaet O, Gujic M, Adamopoulos D, Beloka S, Dreyfuss C, Degaute JP, van de Borne P. Nicotine increases chemoreflex sensitivity to hypoxia in non-smokers. J Hypertension. 2008;26(2):284–94.CrossRef
28.
go back to reference Fernandez R, Larrain C, Zapata P. Acute ventilatory amd circulatory reactions evoked by nicotine: are they excitatory or depressant. Respir Physiol Neurobiol. 2002;133:173–82.CrossRefPubMed Fernandez R, Larrain C, Zapata P. Acute ventilatory amd circulatory reactions evoked by nicotine: are they excitatory or depressant. Respir Physiol Neurobiol. 2002;133:173–82.CrossRefPubMed
29.
go back to reference Yamamoto H, Inaba S, Nishiura Y, Kishi F, Kawakami Y. Acute inhalation of cigarette smoke augments hypoxic chemosensitivity in humans. J Appl Physiol. 1985;58(3):717–23.PubMed Yamamoto H, Inaba S, Nishiura Y, Kishi F, Kawakami Y. Acute inhalation of cigarette smoke augments hypoxic chemosensitivity in humans. J Appl Physiol. 1985;58(3):717–23.PubMed
30.
go back to reference Zapata P, Zuazo A, Llados F. Respiratory and circulatory reflexes induced by nicotine injections: role of carotid body chemoreceptors. Arch Int Pharmacodyn Ther. 1976;219(1):128–39.PubMed Zapata P, Zuazo A, Llados F. Respiratory and circulatory reflexes induced by nicotine injections: role of carotid body chemoreceptors. Arch Int Pharmacodyn Ther. 1976;219(1):128–39.PubMed
32.
go back to reference Molander L, Hansson A, Lunell E. Pharmacokinetics of nicotine in healthy elderly people. Clin Parmacol Ther. 2001;69:57–65.CrossRef Molander L, Hansson A, Lunell E. Pharmacokinetics of nicotine in healthy elderly people. Clin Parmacol Ther. 2001;69:57–65.CrossRef
33.
go back to reference Heitzer T, Brockhoff C, Mayer B, Warnholtz A, Mollnau H, Henne S, Meinertz T, Münzel T. Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers. Circ Res. 2000;86:36–41.CrossRef Heitzer T, Brockhoff C, Mayer B, Warnholtz A, Mollnau H, Henne S, Meinertz T, Münzel T. Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers. Circ Res. 2000;86:36–41.CrossRef
34.
go back to reference Tsuchiya M, Asada A, Kasahara E, Sato EF, Shindo M, Inoue M. Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma. Circulation. 2002;105:1155–7.CrossRefPubMed Tsuchiya M, Asada A, Kasahara E, Sato EF, Shindo M, Inoue M. Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma. Circulation. 2002;105:1155–7.CrossRefPubMed
35.
go back to reference Hildebrandt W, Alexander S, Bärtsch P, Dröge W. Effect of N-acetyl-cysteine on the hypoxic ventilatory response (HVR) and erythropoietin (EPO) production - linkage between plasma thiol redox state and O2 chemosensitivity. Blood. 2002;99(5):1552–5.CrossRefPubMed Hildebrandt W, Alexander S, Bärtsch P, Dröge W. Effect of N-acetyl-cysteine on the hypoxic ventilatory response (HVR) and erythropoietin (EPO) production - linkage between plasma thiol redox state and O2 chemosensitivity. Blood. 2002;99(5):1552–5.CrossRefPubMed
36.
go back to reference Lipton AJ, Johnson MA, Macdonald T, Lieberman MW, Gozal D, Gaston B. S-Nitrosothiols signal the ventilatory response to hypoxia. Nature. 2001;413:171–4.CrossRefPubMed Lipton AJ, Johnson MA, Macdonald T, Lieberman MW, Gozal D, Gaston B. S-Nitrosothiols signal the ventilatory response to hypoxia. Nature. 2001;413:171–4.CrossRefPubMed
37.
go back to reference Buyse B, Markous N, Cauberghs M, van Klaveren R, Muls E, Demedts M. Effect of obesity and/or sleep apnea on chemosensitivity: differences between men and women. Respir Physiol Neurobiol. 2003;134:13–22.CrossRefPubMed Buyse B, Markous N, Cauberghs M, van Klaveren R, Muls E, Demedts M. Effect of obesity and/or sleep apnea on chemosensitivity: differences between men and women. Respir Physiol Neurobiol. 2003;134:13–22.CrossRefPubMed
38.
39.
go back to reference Casasola GG, Alvarez-Sala JL, Marques JA, Sanchez-Alarcos JM, Tashkin DP, Espinos D. Cigarette smoking behavior and respiratory alterations during sleep in a healthy population. Sleep Breath. 2002;6(1):19–24.CrossRefPubMed Casasola GG, Alvarez-Sala JL, Marques JA, Sanchez-Alarcos JM, Tashkin DP, Espinos D. Cigarette smoking behavior and respiratory alterations during sleep in a healthy population. Sleep Breath. 2002;6(1):19–24.CrossRefPubMed
40.
go back to reference Urquhart BL, House AA, Cutler MJ, Spence JD, Freeman DJ. Thiol exchange: an in vitro assay that predicts the efficacy of novel homocysteine lowering therapies. J Pharm Sci. 2006;95:1742–50.CrossRefPubMed Urquhart BL, House AA, Cutler MJ, Spence JD, Freeman DJ. Thiol exchange: an in vitro assay that predicts the efficacy of novel homocysteine lowering therapies. J Pharm Sci. 2006;95:1742–50.CrossRefPubMed
41.
go back to reference Pardal R, López-Barneo J. Low glucose-sensing cells in the carotid body. Nat Neurosci. 2002;5(3):197–8.CrossRefPubMed Pardal R, López-Barneo J. Low glucose-sensing cells in the carotid body. Nat Neurosci. 2002;5(3):197–8.CrossRefPubMed
42.
go back to reference Holgert H, Hökfelt T, Hertzberg T, Lagercrantz H. Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Proc Natl Acad Sci U S A. 1995;92(16):7575–9.CrossRefPubMedPubMedCentral Holgert H, Hökfelt T, Hertzberg T, Lagercrantz H. Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Proc Natl Acad Sci U S A. 1995;92(16):7575–9.CrossRefPubMedPubMedCentral
43.
go back to reference Barretto-Filho JAS, Consolim-Colombo FM, Guerra-Riccio GM, Santos RD, Chacra AP, Lopes HF, Teixeira SH, Martinez T, Krieger JE, Krieger EM. Hypercholesterolemia blunts forearm vasorelaxation and enhances the pressure response during acute systemic hypoxia. Arterioscler Thromb Vasc Biol. 2003;23:1660–6.CrossRef Barretto-Filho JAS, Consolim-Colombo FM, Guerra-Riccio GM, Santos RD, Chacra AP, Lopes HF, Teixeira SH, Martinez T, Krieger JE, Krieger EM. Hypercholesterolemia blunts forearm vasorelaxation and enhances the pressure response during acute systemic hypoxia. Arterioscler Thromb Vasc Biol. 2003;23:1660–6.CrossRef
44.
go back to reference Bishop C, Parker GC, Coscina DV. Systemic nicotine alters whole-body fat utilization in female rats. Physiol Behav. 2004;80(4):563–7.CrossRefPubMed Bishop C, Parker GC, Coscina DV. Systemic nicotine alters whole-body fat utilization in female rats. Physiol Behav. 2004;80(4):563–7.CrossRefPubMed
Metadata
Title
Lower hypoxic ventilatory response in smokers compared to non-smokers during abstinence from cigarettes
Authors
Wulf Hildebrandt
Roland Sauer
Ulrich Koehler
Peter Bärtsch
Ralf Kinscherf
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2016
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-016-0323-0

Other articles of this Issue 1/2016

BMC Pulmonary Medicine 1/2016 Go to the issue