Effects of a novel benzodiazepine derivative, JM-1232(-), on human gastroepiploic artery in vitro.
J Cardiothorac Vasc Anesth, 2011/2;25(1):72-7.
Moriyama T[1], Tsuneyoshi I, Kanmura Y
Affiliations
PMID: 20599400DOI: 10.1053/j.jvca.2010.03.013
Impact factor: 2.894
Abstract
objective: To investigate the effects of JM-1232(-) on norepinephrine (10(-6) mol/L)- and high K(+) (40 mmol/L)-induced contractions in isolated human gastroepiploic arteries (GEA), and to compare them with the effects of midazolam and propofol. In addition, to investigate whether the benzodiazepine-receptor antagonist, flumazenil, or μ-opioid-receptor antagonist, naloxone, influenced the vascular effects of JM-1232(-).
design: An in vitro experimental study.
setting: University laboratory.
participants: GEA segments were used from 69 patients undergoing coronary artery bypass graft surgery.
measurements and main results: JM-1232(-) produced dose-dependent relaxation effects in the rings. Although these effects of JM-1232(-) were greater than those of midazolam and propofol at high concentrations (10(-5)-10(-4) mol/L), there were no significantly different relaxation effects at the clinical concentrations of 3 × 10(-6) mol/L JM-1232(-), 3 × 10(-6) mol/L midazolam, and 1 × 10(-5) mol/L propofol. In addition, all these effects were independent of the presence of a functional endothelium. Vasorelaxation induced by JM-1232(-) on norepinephrine-preconstricted GEA was inhibited by flumazenil, but not by naloxone.
conclusions: These results indicate that JM-1232(-) dose-dependently relaxes smooth muscle in human GEA, this effect being independent of the endothelium. Within the ranges of plasma concentrations achieved in clinical practice, JM-1232(-) had similar vasorelaxation effects to midazolam and propofol. JM-1232(-)-induced vasorelaxation was inhibited by flumazenil, indicating that JM-1232(-)-induced vasorelaxation occurred via peripheral benzodiazepine receptor activation in the GEA.
MeSH terms
Dose-Response Relationship, Drug; Endothelium, Vascular; Flumazenil; GABA Modulators; Gastroepiploic Artery; Humans; In Vitro Techniques; Isoindoles; Midazolam; Muscle Contraction; Muscle, Smooth, Vascular; Naloxone; Narcotic Antagonists; Norepinephrine; Piperazines; Potassium; Propofol; Structure-Activity Relationship; Vasoconstrictor Agents
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