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


CONCLUSIONS
Both clonidine and dexmedetomidine can relax the airway even in the hyper-reactive state.
Yamakage
M
M
Sapporo Medical University School of Medicine, Department of Anesthesiology, Sapporo, Hokkaido, Japan. yamakage@sapmed.ac.jp
Iwasaki
S
S
Satoh
J-I
JI
Namiki
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000402:Airway Obstruction / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000517:prevention & control; D002217:Carbachol / Q000494:pharmacology; D003000:Clonidine / Q000627:therapeutic use*; D020927:Dexmedetomidine / Q000627:therapeutic use*; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010047:Ovalbumin / Q000009:adverse effects*; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D002217:Carbachol; D010047:Ovalbumin; D003000:Clonidine; D000109:Acetylcholine