Mechanisms of direct inhibitory action of propofol on uterine smooth muscle contraction in pregnant rats

Background: Although propofol directly inhibits uterine smooth muscle contr action, the mechanisms of this effect are still unknown. The current study aimed to clarify the mechanisms of the inhibitory effect of propofol on oxy tocin-induced uterine smooth muscle contraction by measuring (1)the concent ration of intracellular free Ca2+ ([Ca2+](i)) simultaneously with muscle te nsion, (2) the amount of intracellular inositol 1,4,5-triphosphate ([IP3](i )), and (3) voltage-dependent Ca2+ channel (VDCC) activity. Methods: Uterine smooth muscle tissues were obtained from pregnant rats (in late gestation). [Ca2+](i) with isometric tension was monitored by the 500 -nm light emission ratio of preloaded Ca2+ indicator fura-2. [IP3](i) and V DCC activity were measured by radioimmunoassay and patch clamp techniques, respectively. The uterine smooth muscle was stimulated by 20 nm oxytocin an d exposed to propofol (10(-7) similar to 10(-4) M). Results: Propofol had significant inhibitory effects on oxytocin-induced ut erine smooth muscle contraction and increased [Ca2+]i in pregnant rats in a dose-dependent manner, without affecting the agonist-receptor binding affi nity. Propofol inhibited the increase in [IP3](i) induced by oxytocin. Prop ofol also inhibited VDCC activity in both activated and inactivated states. The solvent Intralipid((R)) had no effects on these parameters. Conclusions: Propofol inhibits oxytocin-induced uterine smooth muscle contr action, at least in part, by decreasing [Ca2+](i) without affecting agonist -receptor binding; the inhibitory effect of propofol on [Ca2+](i) might be mediated both by a decrease in [IP3](i) and by inhibition of VDCC activity.