Y-27632 augments the isoflurane-induced relaxation of bronchial smooth muscle in rats.
Recent studies revealed an involvement of RhoA/Rho-kinase signaling in the agonist-induced Ca(2+) sensitization of bronchial smooth muscle contraction, and the pathway has now been proposed as a new target for the treatment of airway obstructive diseases, such as asthma. On the other hand, volatile anesthetics such as isoflurane are traditionally used to treat status asthmaticus. In the present study, the effect of inhibition of Rho-kinase on the isoflurane-induced relaxation of bronchial smooth muscle was investigated. Smooth muscle strips of intrapulmonary bronchi obtained from Wistar rats were used. Application of isoflurane (0.5-4.0%, generated by a calibrated vaporizer) to the acetylcholine (30 microM)-precontracted rat bronchial smooth muscles caused a concentration-dependent relaxation. Interestingly, the isoflurane-induced relaxation was significantly augmented by the pretreatment with subthreshold concentration of Y-27632, a Rho-kinase inhibitor. Thus, the combined use of Y-27632 and isoflurane might be useful for treatment of severe airway blockade, such as status asthmaticus.
Hanazaki
Motohiko
M
Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan. motohiko@hanazaki.com
Chiba
Yoshihiko
Y
Yokoyama
Masataka
M
Morita
Kiyoshi
K
Kohjitani
Atsushi
A
Sakai
Hiroyasu
H
Misawa
Miwa
M
D000109:Acetylcholine / Q000009:adverse effects; D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007530:Isoflurane / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000577:Amides; D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D007530:Isoflurane; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000109:Acetylcholine