Agonist-dependent smooth muscle contraction results in Ca²⁺ sensitisation of the myofilaments by activation of an intracellular signalling cascade involving rho-associated kinase (ROK). Hyperstimulation of this pathway has been implicated in the increased vascular tone of hypertension, and the development of arteriosclerosis, in animal models (e.g. Shimokawa et al. 2001). Enhanced ROK activation may, therefore, contribute to the increased vascular resistance associated with pregnancy-related disorders such as pre-eclampsia. However, the involvement of ROK activation in contractility of arteries from pregnant women or term fetuses is unknown. Therefore, in this study, we have examined the ability of ROK inhibitors, Y-27632 (Ueheta et al. 1997) or HA1077 (Sward et al. 2000), to alter agonist-dependent contractions of human maternal and fetal arteries.

Omental arteries (from term pregnant women undergoing elective Caesarean section) and placental chorionic plate arteries (from women undergoing normal vaginal delivery at term) were isolated from biopsies obtained following written informed consent according to local ethical committee guidelines. Vessels were normalised on a wire myograph (37°C, 95 % air-5 % CO₂) and constricted with ~EC₇₀ dose of the thromboxane mimetic U46619 (100 nM) and exposed to incremental doses (0.1-10 µM) of Y-27632 or HA1077.

Placental arterial constrictions to U46619 were reduced in a dose-dependent manner with 10 µM Y-27632 attenuating contractions to 53 ± 11 % (mean ± S.E.M., P < 0.05, Student’s paired t test, n = 5) of control. However, HA1077 was without effect (contractions were 93 ± 6 % of control). Similarly, omental arterial constrictions were inhibited in a concentration-dependent fashion with 10 µM Y-27632 significantly reducing contractions to 19 ± 5 % of control (n = 5). Omental contractions in the presence of HA1077 were 60 ± 15 % (n = 4) of control. Y-27632 appeared to be a more potent inhibitor of agonist-dependent contractions in intact placental and omental arteries than HA1077 consistent with an increased affinity of Y-27632 for ROK over HA1077 (Ueheta et al. 1997; Sward et al., 2000). Western blot analysis of placental and arterial tissue homogenates illustrated both ROK isoforms (α and β) to be present.

These data therefore suggest that ROK activation may play a role in agonist-mediated contraction of human adult and placental arteries.

This work was supported by Tommy’s, the Baby Charity.