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The effect of fasudil, Rhoa/Rho-kinase inhibitor, on phenylephrine-induced contractions in lung strips of chronic ethanol treated-mice Recent studies indicated that the RhoA/Rho-kinase pathway plays an important role in the contraction of smooth muscle and is involved in Ca2+ sensitization (Uehata et al., 1997; Somlyo et al., 1998). The Ca2+ sensitization plays an important role in maintenance of the contractile response to in airway smooth muscle (Yoshii et al., 1999). RhoA/Rho-kinases are expressed in rat bronchial smooth muscle (Chiba et al., 1999), and participate in contraction to phenylephrine, endothelin, angiotensin and norepinephrine. Several factors modulate bronchial smooth muscle contraction signaling associated with the RhoA/Rho-kinase pathway. However, to our knowledge, it has not yet been investigated the effect of chronic ethanol treatment on the Rho-kinase pathway in the lung. Therefore, in the present study, the effect of chronic ethanol treatment on the phenylephrine-induced contractions of lung strips was investigated in mice. Phenylephrine (10-8-10-4 M) and KCl (10-80 mM) induced concentration-dependent contractions in lungs strips. Chronic-ethanol treatment (14 days) significantly inhibited contractions to phenylephrine compared to the control group. Fasudil (10-4 M) induced relaxation in the lung tissues contracted with phenylephrine. In ethanol treatment groups, fasudil (10-4 M)-induced relaxations were significantly decreased. These results suggest that chronic ethanol treatment may cause desensitization to contraction with phenylephrine and relaxation with fasudil in lung strips of mice, and this phenomenon may involve the RhoA/Rho-kinase pathway. |
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