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. 1999 Nov;54(11):1033–1035. doi: 10.1136/thx.54.11.1033

Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma

H W F M de Gouw 1, M Verbruggen 1, I Twiss 1, P Sterk 1
PMCID: PMC1745401  PMID: 10525564

Abstract

BACKGROUND—Nitric oxide (NO) may exert protective properties within the airways of asthmatic patients. It was postulated that airways obstruction in asthma may be associated with endogenous NO deficiency caused by limited availability of NO synthase substrate.
METHODS—In a double blind, crossover study 14 asthmatic patients received pretreatment with oral L-arginine (50 mg/kg body weight) or placebo prior to histamine challenge. Histamine challenge was performed until a 50% fall in forced expiratory volume in one second (FEV1) occurred and the response was expressed as the provocative concentration causing a 20% fall in FEV1 (PC20) and as the dose-response slope (maximal % fall in FEV1/cumulative dose (µmol)).
RESULTS—Pretreatment with L-arginine did not affect PC20 histamine (mean change in doubling dose 0.18 (95% confidence interval (CI) -0.36 to 0.71), p = 0.5) but the dose-response slope to histamine was slightly reduced (mean change: 0.7 (95% CI 0.6 to 0.9), p= 0.016).
CONCLUSIONS—Oral L-arginine does not influence airway hyperresponsiveness to histamine as reflected by PC20, although the dose-response slope is slightly reduced in patients with asthma. This indicates only marginal, clinically unimportant limitation of NO synthase substrate in asthma.



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Selected References

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  1. Chakder S., Rattan S. L-arginine deficiency causes suppression of nonadrenergic noncholinergic nerve-mediated smooth muscle relaxation: role of L-citrulline recycling. J Pharmacol Exp Ther. 1997 Jul;282(1):378–384. [PubMed] [Google Scholar]
  2. Chang C. I., Liao J. C., Kuo L. Arginase modulates nitric oxide production in activated macrophages. Am J Physiol. 1998 Jan;274(1 Pt 2):H342–H348. doi: 10.1152/ajpheart.1998.274.1.H342. [DOI] [PubMed] [Google Scholar]
  3. Folkerts G., van der Linde H. J., Nijkamp F. P. Virus-induced airway hyperresponsiveness in guinea pigs is related to a deficiency in nitric oxide. J Clin Invest. 1995 Jan;95(1):26–30. doi: 10.1172/JCI117649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Massaro A. F., Gaston B., Kita D., Fanta C., Stamler J. S., Drazen J. M. Expired nitric oxide levels during treatment of acute asthma. Am J Respir Crit Care Med. 1995 Aug;152(2):800–803. doi: 10.1164/ajrccm.152.2.7633745. [DOI] [PubMed] [Google Scholar]
  5. Nijkamp F. P., van der Linde H. J., Folkerts G. Nitric oxide synthesis inhibitors induce airway hyperresponsiveness in the guinea pig in vivo and in vitro. Role of the epithelium. Am Rev Respir Dis. 1993 Sep;148(3):727–734. doi: 10.1164/ajrccm/148.3.727. [DOI] [PubMed] [Google Scholar]
  6. O'Connor G., Sparrow D., Taylor D., Segal M., Weiss S. Analysis of dose-response curves to methacholine. An approach suitable for population studies. Am Rev Respir Dis. 1987 Dec;136(6):1412–1417. doi: 10.1164/ajrccm/136.6.1412. [DOI] [PubMed] [Google Scholar]
  7. Perez A. C., Paul W., Harrison S., Page C. P., Spina D. The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro. Braz J Med Biol Res. 1998 Jun;31(6):811–818. doi: 10.1590/s0100-879x1998000600014. [DOI] [PubMed] [Google Scholar]
  8. Ricciardolo F. L., Di Maria G. U., Mistretta A., Sapienza M. A., Geppetti P. Impairment of bronchoprotection by nitric oxide in severe asthma. Lancet. 1997 Nov 1;350(9087):1297–1298. doi: 10.1016/s0140-6736(05)62474-9. [DOI] [PubMed] [Google Scholar]
  9. Rogers N. E., Ignarro L. J. Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine. Biochem Biophys Res Commun. 1992 Nov 30;189(1):242–249. doi: 10.1016/0006-291x(92)91550-a. [DOI] [PubMed] [Google Scholar]
  10. Taylor D. A., McGrath J. L., Orr L. M., Barnes P. J., O'Connor B. J. Effect of endogenous nitric oxide inhibition on airway responsiveness to histamine and adenosine-5'-monophosphate in asthma. Thorax. 1998 Jun;53(6):483–489. doi: 10.1136/thx.53.6.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. de Boer J., Meurs H., Coers W., Koopal M., Bottone A. E., Visser A. C., Timens W., Zaagsma J. Deficiency of nitric oxide in allergen-induced airway hyperreactivity to contractile agonists after the early asthmatic reaction: an ex vivo study. Br J Pharmacol. 1996 Nov;119(6):1109–1116. doi: 10.1111/j.1476-5381.1996.tb16011.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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