Evaluation of Y-27632, a Rho-kinase inhibitor, as a bronchodilator in guinea pigs

To evaluate (+)-(R)-trans-4-(1-Aminoethyl)-N-(4-pyridyl) cyclohexanecarboxa mide dihydrochloride, monohydrate (Y-27632), a selective Rho-kinase inhibit or, as a novel bronchodilator in vivo and in vitro, we investigated the eff ect 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 acetylchol ine- or ovalbumin-induced contraction of isolated trachea. Y-27632 inhalati on (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 t he acetylcholine- or ovalbumin-induced contraction of isolated trachea with rank order of potency, salbutamol > Y-27632 > theophylline. The relaxant e ffect of Y-27632 was not affected by propranolol. We conclude that, althoug h Y-27632 is not as potent as a beta-adrenoceptor agonist, Y-27632 may beco me an alternative inhaled bronchodilator, because Y-27632 is more potent th an theophylline, and the relaxant effect is independent of beta-adrenocepto rs. (C) 2000 Elsevier Science B.V. All rights reserved.