Antioxidant effect of muscle relaxants (vecuronium, rocuronium) on the rabbit abdominal aortic endothelial damage induced by reactive oxygen species

Abstract

Background: Muscle relaxants induce vascular smooth muscle relaxation by inducing synthesis of the prostaglandins that influence vasomotor tone. However, the effects of muscle relaxants on endothelial cells and tissues following injury by reactive oxygen species (ROS) are unclear. We tested the effects of the muscle relaxants vecuronium and rocuronium on impaired acetylcholine (ACh)-induced relaxation following induction of ROS in rabbit aorta in vitro. Methods: Isolated rabbit abdominal aortic ring segments were pretreated with vecuronium or rocuronium at 10-4, 3 × 10-4, 10-3 or 3 × 10-3 M, with or without inhibitors of Cu/Zn superoxide dismutase (diethyldithiocarbamate; DETCA, 0.8 mM) or catalase (3-amino-1,2,4-triazole; 3AT, 50 mM). All groups of aortic rings were then exposed to ROS gener-ated by electrolysis in the organ bath medium (Krebs-Henseleit solution). The effects of vecuronium and rocuronium on ROS-induced impairment of relaxation induced by ACh (10-6 M) were assessed. Results: Aortic rings treated with vecuronium or rocuronium at 10-4, 3 × 10-4, 10-3 or 3 × 10-3 M preserved the capacity for ACh-induced endothelial relaxation following ROS exposure in a dose-dependent manner. Pretreatment with DET-CA partially inhibited the protective effects of vecuronium and rocuronium on ACh-induced relaxation (P < 0.001), but pretreatment with 3AT had no effect. Conclusions: Muscle relaxants protected the endothelium in isolated rabbit abdominal aorta from free-radical injury in a dose-dependent manner. These results suggest that vecuronium and rocuronium may act as superoxide anion scaven-gers.