Small arteries of gestational rats are less sensitive to relaxation induced by inhibition of rho A‐associated kinase (ROK).

Abstract

Inhibition of ROK has been proposed as a method to arrest uterine contractions during preterm labor. Because of concern about vascular side effects, we studied the effects of the ROK inhibitor g‐H1152 (g‐H) on relaxation of mesenteric and uterine arteries.Arteries from non‐pregnant (n=5) and pregnant (gestation day17–21; n=6) rats were studied using wire myography. Concentration response curves (CRC) to calculate IC50 for g‐H were obtained following phenylephrine (PE) or endothelin‐1 (ET‐1) induced constriction. Using vessels from pregnant rats, CRC for PE were performed before and after a 20‐min incubation with g‐H at 300 nM, 1 and 3 μM.Mesenteric arteries were more sensitive than uterine arteries to g‐H‐induced relaxation in both non‐pregnant and pregnant rats. Both arteries were significantly less sensitive to g‐H‐induced relaxation during pregnancy. Sensitivity to PE was not changed with any dose of g‐H. However, using 2‐factor ANOVA, the maximal PE‐induced tension was significantly reduced by the two highest concentrations of g‐H in both vessels from pregnant rats but to a greater extent in mesenteric vessels (34±5.6%, 18±4.1%) compared to uterine (14±4%, 7±2.7%).The ROK pathway plays a significant role in agonist‐induced constriction of mesenteric and uterine vessels, though less so during gestation. If ROK inhibitors are used during pregnancy in vivo, maternal blood pressure and uterine blood flow will be assessed.