The involvement of Rho-associated kinases in agonist-dependent contractions of human maternal and placental arteries at term gestation.

Abstract

The purpose of this study was to assess the involvement of rho kinase (ROK) in agonist-dependent contraction of omental, myometrial, and placental arteries of pregnant women at term. Wire myography was used to assess if contractions of intact or alpha-toxin-permeabilized arteries obtained from women at elective cesarean section were influenced by the ROK inhibitor Y-27632. Western blotting indicated the presence of ROKalpha in each of the 3 tissue types. In intact human omental, myometrial, or placental arteries, Y-27632 dose-dependently reduced constrictions to the thromboxane-mimetic U46619. In permeabilized vessels, U46619 induced substantial Ca(2+)-sensitization of contraction that was inhibited by Y27632. The phosphatase inhibitor calyculin A induced a Ca(2+)sensitization of contraction similar to that of U46619 in permeabilized omental arteries that was unaffected by Y-27632, suggesting that ROK may signal via myosin phosphatase in these vessels. These results are the first report of the involvement of ROK in the receptor-coupled constriction of intact and permeabilized arteries from pregnant women.