Investigation of the relaxant effects of propofol on ovalbumin-induced asthma in guinea pigs.
OBJECTIVE
Because the incidence of asthma appears to be increasing, the importance of proper perioperative management of individuals with asthma will also continue to increase. Although its mechanism of smooth muscle relaxation is unknown, propofol has been associated with less bronchoconstriction during anaesthetic induction. The aim of this study was to investigate the possible mechanism of these effects and the effects of propofol on the isolated trachea preparations from control and ovalbumin-sensitized guinea pigs.


METHODS
Adult male guinea pigs, weighing 280-330 g, were randomly allocated to two experimental groups, each consisting of 10 animals. Ten guinea pigs were sensitized by intramuscular injections of 0.30 mL of a 5% (w/v) ovalbumin/saline solution into each thigh (0.6 mL total) on days 1 and 4, whereas the remaining 10 served as controls receiving a total of 0.6 mL distilled water on days 1 and 4 as placebo. The isolated trachea preparations were mounted in tissue baths with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. We tested the effects of propofol (10(-7)-10(-3) M) on resting tension and after precontraction with carbachol and histamine on isolated trachea preparations from control and ovalbumin-sensitized guinea pigs. We also tested the effect of propofol on isolated trachea preparations precontracted with carbachol and histamine in the absence and presence of different inhibitors or antagonists. We investigated propofol responses in tracheal smooth muscle precontracted with CaCl2.


RESULTS
Propofol (10(-7)-10(-3) M) produced a concentration-dependent relaxation of isolated tracheal preparations precontracted by carbachol (10(-6) M) and histamine (10(-6) M) in both groups. Preincubation with N(w)-nitro L-arginine methyl ester (3x10(-5) M), indomethacin (10(-5) M) or propranolol (10(-4) M) did not produce a significant alteration on propofol-induced relaxation responses (P>0.05), while preincubation with tetraethylammonium (3x10(-4) M) significantly decreased the propofol-induced relaxation responses in both groups (P<0.05). Propofol (10(-7)-10(-3) M) induced concentration-dependently relaxations in isolated trachea rings precontracted with CaCl2 in both the control and ovalbumin-sensitized groups.


CONCLUSIONS
Propofol induced concentration-dependent relaxations in precontracted, isolated trachea smooth muscle of guinea pigs in both the control and ovalbumin-sensitized groups. These relaxations were independent of epithelial function and stimulation of beta adrenergic receptors. Opened Ca2+-sensitive K+ channels and inhibited L-type Ca2+ channels can contribute to these relaxations.
Bagcivan
I
I
Cumhuriyet University School of Medicine, Department of Pharmacology, Sivas, Turkey. ibagcivan@cumhuriyet.edu.tr
Cevit
O
O
Yildirim
M K
MK
Gursoy
S
S
Yildirim
S
S
Kaya
T
T
Mimaroglu
C
C
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D015220:Calcium Channels / Q000187:drug effects; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D010047:Ovalbumin; D015221:Potassium Channels / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D011897:Random Allocation; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D015220:Calcium Channels; D006993:Hypnotics and Sedatives; D015221:Potassium Channels; D009569:Nitric Oxide; D010047:Ovalbumin; D015742:Propofol