• Anesthesiology · Mar 2005

    Ketamine attenuates acetylcholine-induced contraction by decreasing myofilament Ca2+ sensitivity in pulmonary veins.

    • Xueqin Ding, Derek S Damron, and Paul A Murray.
    • Center for Anesthesiology Research, The Cleveland Clinic Foundation, The Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Ohio 44195, USA.
    • Anesthesiology. 2005 Mar 1; 102 (3): 588-96.

    BackgroundThe authors investigated the extent and cellular mechanisms by which the intravenous anesthetic ketamine alters acetylcholine-induced contraction in pulmonary veins (PVs). They tested the hypothesis that ketamine inhibits acetylcholine contraction in PVs.MethodsCanine PV rings with endothelium (E+) and without endothelium (E-) were isolated for measurement of isometric tension. The effects of ketamine (10(-5) m approximately 10(-3) m) on acetylcholine contraction were assessed in E+ and E- rings. The effects of inhibiting nitric oxide synthase on ketamine-induced changes in acetylcholine contraction were investigated in E+ rings, whereas the effects of Ca2+ influx and Ca2+ release were investigated in E- rings. In fura-2 loaded E- PV strips, the effects of ketamine (10(-4) m) on the intracellular Ca2+ concentration-tension relation (i.e., myofilament Ca sensitivity) were assessed in the presence or absence of acetylcholine. The roles of the protein kinase C and rho-kinase signaling pathways in ketamine-induced changes in myofilament Ca2+ sensitivity were also investigated.ResultsKetamine caused dose-dependent (P < 0.001) inhibition of acetylcholine contraction in E+ and E- PV rings. The ketamine-induced attenuation of acetylcholine contraction was still observed after inhibition of nitric oxide synthase (P = 0.002), Ca2+ influx (P < 0.001), and Ca2+ release (P = 0.021). Ketamine alone had no effect on myofilament Ca2+ sensitivity (P = 0.892) but attenuated (P = 0.038) the acetylcholine-induced increase in myofilament Ca2+ sensitivity. This attenuation was still observed after rho-kinase inhibition (P = 0.039), whereas it was abolished by protein kinase C inhibition (P = 0.798).ConclusionsKetamine attenuates acetylcholine contraction by inhibiting the acetylcholine-induced increase in myofilament Ca2+ sensitivity, which is mediated by the protein kinase C signaling pathway.

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