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Keywords:

  • Ca2+ sensitization;
  • cerebral artery;
  • thromboxane A2;
  • myosin light chain;
  • myosin light chain kinase;
  • Rho kinase
  • The role of Rho kinase in Ca2+ sensitization of the contractile apparatus in smooth muscle was investigated in the bovine middle cerebral artery.

  • U46619, a thromboxane A2 analog, induced a greater sustained contraction with a smaller [Ca2+]i elevation than that seen with 118 mM K+. The level of myosin light chain (MLC) phosphorylation obtained in the initial phase of the contraction was higher than that seen with 118 mM K+; thereafter, it gradually declined to a comparable level in the late phase.

  • During the steady state of the U46619-induced contraction, Y27632 (10 μM), a Rho-kinase inhibitor, partially inhibited [Ca2+]i, although it substantially inhibited tension and MLC phosphorylation. Wortmannin (10 μM), an MLC kinase inhibitor, had no significant effect on [Ca2+]i, but it completely inhibited MLC phosphorylation and partially inhibited tension. The wortmannin-resistant tension development was thus not associated with MLC phosphorylation, and this component was completely inhibited by Y27632.

  • In conclusion, U46619 enhanced Ca2+ sensitivity in a manner both dependent and independent of MLC phosphorylation in the bovine middle cerebral artery. Both mechanisms of Ca2+ sensitization can be inhibited by the Rho-kinase inhibitor.

British Journal of Pharmacology (2003) 140, 871–880. doi:10.1038/sj.bjp.0705487