Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-28T01:03:53.287Z Has data issue: false hasContentIssue false
  • English
  • Français

Inhibitory effects of the alpha-2 adrenergic agonists clonidine and dexmedetomidine on enhanced airway tone in ovalbumin-sensitized guinea pigs

Published online by Cambridge University Press:  01 January 2008

M. Yamakage ,
S. Iwasaki ,
J.-I. Satoh  and
A. Namiki
M. Yamakage*
Affiliation:
Sapporo Medical University School of Medicine, Department of Anesthesiology, Sapporo, Hokkaido, Japan
S. Iwasaki
Affiliation:
Sapporo Medical University School of Medicine, Department of Anesthesiology, Sapporo, Hokkaido, Japan
J.-I. Satoh
Affiliation:
Sapporo Medical University School of Medicine, Department of Anesthesiology, Sapporo, Hokkaido, Japan
A. Namiki
Affiliation:
Sapporo Medical University School of Medicine, Department of Anesthesiology, Sapporo, Hokkaido, Japan
*
Correspondence to: Michiaki Yamakage, Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan. E-mail: [email protected]; Tel: +81 11 611 2111, ext. 3568; Fax: +81 11 631 9683
Get access

Summary

Background and objective

The alpha-2 adrenergic agonists clonidine and dexmedetomidine are used as an antihypertensive and a sedative, respectively. The aim of this study was to determine the effects of these agonists on ovalbumin-sensitized airway tone in guinea pigs.

Methods

The animals were divided into two groups: control and sensitized. The sensitized group received ovalbumin intraperitoneally and was boosted by exposure to aerosolized ovalbumin. The effects of the alpha-2 agonists were investigated by measuring (1) total lung resistance and (2) smooth muscle tension using a tracheal ring preparation.

Results

In the control group, acetylcholine significantly increased total lung resistance in a dose-dependent manner. In the sensitized animals, total lung resistance was significantly higher (by 95%) at 6 μg kg−1 acetylcholine than that in the control group. Both clonidine and dexmedetomidine had a slight but significant inhibitory effect on the response curve of lung resistance at higher concentrations of carbachol, a potent muscarinic receptor agonist. Similar to the data obtained in the control group, both clonidine and dexmedetomidine significantly decreased total lung resistance and the inhibitory effects of these alpha-2 agonists on lung resistance were significantly distinguishable. Similar direct inhibitory effects of the alpha-2 agonists on carbachol-induced muscle contraction were observed in both the control and sensitized groups, the inhibitory effects in the sensitized group being significantly greater.

Conclusion

Both clonidine and dexmedetomidine can relax the airway even in the hyper-reactive state.

Keywords

RECEPTORS ADRENERGIC ALPHA-2CLONIDINEDEXMEDETOMIDINEOVALBUMINAIRWAY RESISTANCE
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 1 , January 2008 , pp. 67 - 71
Copyright
Copyright © European Society of Anaesthesiology 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This paper was presented in part at the annual meeting of the American Society of Anesthesiologists, Las Vegas, NV, USA, October 23–27, 2004 and at the annual meeting of the American Society of Anesthesiologists, Atlanta, GA, October 22–26, 2005.

References

1.Wright, PM, Carabine, UA, McClune, S et al. . Preanaesthetic medication with clonidine. Br J Anaesth 1990; 65: 628–632.CrossRefGoogle ScholarPubMed
2.Engelman, E, Lipszyc, M, Gilabrt, E et al. . Effects of clonidine on anesthetic drug requirements and hemodynamic response during aortic surgery. Anesthesiology 1989; 71: 178–187.CrossRefGoogle ScholarPubMed
3.Douglas, BC, Drew, BC, Grald, AM. Dexmedetomidine. Curr Opin Crit Care 2001; 7: 221–226.Google Scholar
4.Venn, RM, Newman, PJ, Grounds, RM. A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med 2003; 29: 201–207.CrossRefGoogle ScholarPubMed
5.Munoz, NM, Leff, AR. Evidence for two sybtypes of alpha adrenergic receptors in canine airway smooth muscle. J Pharmacol Exp Ther 1981; 217: 530–535.Google Scholar
6.Advenier, C, Floch, A, Mallard, B. Bronchopulmonary effects of clonidine on the bronchomotor responses of the guinea-pig. Eur J Pharmacol 1983; 89: 85–94.CrossRefGoogle ScholarPubMed
7.Takayanagi, I, Kawano, K, Koike, K. Alpha 2-adrenoceptor mechanisms in guinea-pig trachea. Eur J Pharmacol 1990; 182: 577–580.CrossRefGoogle ScholarPubMed
8.Arimitsu, M, Mitsui-Saito, M, Sato, K et al. . Mechanism of relaxant of clonidine in isolated bovine tracheal smooth muscle. J Pharmacol Exp Ther 1998; 286: 681–687.Google Scholar
9.Yu, M, Wang, Z, Robinson, N. Prejunctional alpha 2-adrenoceptors inhibit acetylcholine release from cholinergic nerves in equine airways. Am J Physiol 1993; 265: L565–L570.Google ScholarPubMed
10.Manning, MM, Broadstone, RV. Effects of alpha 2-adrenergic receptor agonist and antagonist drugs on cholinergic contraction in bovine tracheal smooth muscle in vitro. Am J Vet Res 1995; 56: 930–935.Google Scholar
11.Groeben, H, Mitzner, W, Brown, RH. Effects of the alpha 2-adrenoceptor agonist dexmedetomidine on bronchoconstriction in dogs. Anesthesiology 2004; 100: 359–363.CrossRefGoogle Scholar
12.Boskabady, MH, Adel-Kardan, S. Increased muscarinic receptor blockade by atropine in tracheal chains of ovalbumin-sensitized guinea pigs. Pharmacology 1999; 58: 300–308.CrossRefGoogle ScholarPubMed
13.Toward, TJ, Broadley, KJ. Early and late bronchoconstrictions, airway hyperreactivity, leucocyte influx and lung histamine and nitric oxide after inhaled antigen: Effects of dexamethasone and rolipram. Clin Exp Allergy 2004; 34: 91–102.Google Scholar
14.Sakurada, T, Abe, M, Kodani, M et al. . Synergistic effects of pranlukast and a leukotriene B4 receptor antagonist on antigen-induced pulmonary reaction. Eur J Pharmacol 1999; 370: 153–159.CrossRefGoogle Scholar
15.Iwasaki, S, Yamakage, M, Satoh, J-I, Namiki, A. Different inhibitory effects of sevoflurane on hyperreactive airway smooth muscle contractility in ovalbumin-sensitized and chronic cigarette-smoking guinea pig models. Anesthesiology 2006; 105: 753–763.CrossRefGoogle ScholarPubMed
16.Talke, P, Chen, R, Thomas, B et al. . The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000; 90: 834–839.CrossRefGoogle ScholarPubMed
17.Tudoric, N, Coon, RL, Kampine, JP, Bosnjak, ZJ. Effects of halothane and isoflurane on antigen- and leukotriene-D4-induced constriction of guinea-pig trachea. Acta Anaesthesiol Scand 1995; 39: 1111–1116.Google Scholar
18.Ikegami, K, Hata, H, Fuchigami, J-I et al. . Apafant (a PAF receptor antagonist) suppresses the early and late airway responses in guinea pigs: a comparison with antiasthmatic drugs. Eur J Pharmacol 1997; 328: 75–81.CrossRefGoogle ScholarPubMed
19.Bagcivan, I, Cevit, O, Yildirim, MK et al. . Investigation of the relaxant effect of propofol on ovalbumin-induced asthma in guinea pigs. Eur J Anaesthesiol 2007; 24: 796–802.Google Scholar
20.Gal, TJ, Suratt, PM. Resistance to breathing in healthy subjects following endotracheal intubation under topical anesthesia. Anesth Analg 1980; 59: 270–274.CrossRefGoogle ScholarPubMed
21.Guler, G, Akin, A, Tosun, Z et al. . Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubation. Acta Anaesthesiol Scand 2005; 49: 1088–1091.CrossRefGoogle ScholarPubMed
22.O’Connell, F, Thomas, VE, Fuller, RW et al. . Effect of clonidine on induced cough and bronchoconstriction in guinea pigs and healthy humans. J Appl Physiol 1994; 76: 1082–1087.Google Scholar
23.Dinh Xuan, AT, Lockhart, A. Bronchial effects of alpha 2-adrenoceptor agonists and of other antihypertensive agents in asthma. Am J Med 1989; 87: 34S–37S.CrossRefGoogle ScholarPubMed
24.Shibata, O, Saito, M, Hashimoto, S et al. . Clonidine attenuates the carbachol-induced contractile and phosphatidylinositol response of rat trachea. J Pharm Pharmacol 2000; 52: 1523–1528.CrossRefGoogle ScholarPubMed