Evaluation of Y-27632, a rho-kinase inhibitor, as a bronchodilator in guinea pigs.
To evaluate (+)-(R)-trans-4-(l-Aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632), a selective Rho-kinase inhibitor, as a novel bronchodilator in vivo and in vitro, we investigated the effect of Y-27632 on the acetylcholine- or ovalbumin-induced increase in lung resistance (R(L)) in non-sensitized or passively sensitized guinea pigs, and the relaxant effects of salbutamol, Y-27632 and theophylline on acetylcholine- or ovalbumin-induced contraction of isolated trachea. Y-27632 inhalation (1 mM, 2 min) inhibited acetylcholine- or ovalbumin-induced increase in R(L) without changes in mean blood pressure, and the effect persisted for at least 3 h. Salbutamol, Y-27632 and theophylline each completely reversed the acetylcholine- or ovalbumin-induced contraction of isolated trachea with rank order of potency, salbutamol>Y-27632>theophylline. The relaxant effect of Y-27632 was not affected by propranolol. We conclude that, although Y-27632 is not as potent as a beta-adrenoceptor agonist, Y-27632 may become an alternative inhaled bronchodilator, because Y-27632 is more potent than theophylline, and the relaxant effect is independent of beta-adrenoceptors.
Iizuka
K
K
First Department of Internal Medicine, Gunma University Faculty of Medicine, School of Medicine, 3-39-15 Showa-machi, Maebashi, 371-8511, Gunma, Japan. iizukak@showa.gunma-u.ac.jp
Shimizu
Y
Y
Tsukagoshi
H
H
Yoshii
A
A
Harada
T
T
Dobashi
K
K
Murozono
T
T
Nakazawa
T
T
Mori
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D054460:rho-Associated Kinases
D000577:Amides; D001993:Bronchodilator Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000109:Acetylcholine