BACKGROUND AND OBJECTIVE: Pancuronium, vecuronium, mivacurium and rocuronium are nondepolarizing neuromuscular blocking agents, which are competitive antagonists against acetylcholine at nicotinic receptors, and considered to have no direct actions on vascular smooth muscle. We aimed to investigate the relaxant effects and possible underlying mechanisms of these agents on isolated rat thoracic aorta. METHODS: The preparations were precontracted with prostaglandin F2alpha (10(-7) mol l(-1)) and pancuronium (10(-7)-10(-4) mol l(-1)), rocuronium (10(-7)-10(-4) mol l(-1)), vecuronium (10(-7)-10(-4) mol l(-1)) and mivacurium (10(-7)-10(-4) mol l(-1)) added at cumulative concentrations in the presence or absence of a prostaglandin synthesis inhibitor, indomethacin (10(-6) M), and a nitric oxide synthesis inhibitor, N(omega)-nitro-L-arginine methylester (3 x 10(-5)). The same protocol was applied to both endothelia (+) and endothelia (-) aortic rings. The preparations precontracted with prostaglandin F2alpha (10(-7) mol l(-1)) were stimulated with electrical field stimulation at a frequency of 10 Hz as square-wave pulses of 50 V (0.2 ms) in the presence of a noradrenaline reuptake inhibitor desipramine (10(-7) mol l(-1)) and a nonselective beta-blocker propranolol (10(-6) mol l(-1)). Drugs were added at ineffective concentration of 10(-7) mol l(-1). Tetrodotoxin (10(-7) mol l(-1)) was added to test whether the changes were dependent on the neuronal response. RESULTS: Pancuronium and rocuronium relaxed aortic rings precontracted by prostaglandin F2alpha in a dose-dependent manner, but vecuronium and mivacurium did not. The relaxation effect of pancuronium and rocuronium was endothelium independent because there was not a significant response difference from the endothelium-denuded group. CONCLUSION: In conclusion, their relaxation effect may be due to an increase in prostaglandin synthesis. The increased relaxation effect of these agents at electrical field stimulation may be by the decreasing effect of noradrenaline reuptake from nerve endings because a noradrenaline reuptake inhibitor desipramine did not change this effect. Also, these neuromuscular agents may affect beta-receptors, because a nonselective beta-blocker agent, propranolol, decreased their electrical field stimulation-induced relaxations.
BACKGROUND AND OBJECTIVE:Pancuronium, vecuronium, mivacurium and rocuronium are nondepolarizing neuromuscular blocking agents, which are competitive antagonists against acetylcholine at nicotinic receptors, and considered to have no direct actions on vascular smooth muscle. We aimed to investigate the relaxant effects and possible underlying mechanisms of these agents on isolated rat thoracic aorta. METHODS: The preparations were precontracted with prostaglandin F2alpha (10(-7) mol l(-1)) and pancuronium (10(-7)-10(-4) mol l(-1)), rocuronium (10(-7)-10(-4) mol l(-1)), vecuronium (10(-7)-10(-4) mol l(-1)) and mivacurium (10(-7)-10(-4) mol l(-1)) added at cumulative concentrations in the presence or absence of a prostaglandin synthesis inhibitor, indomethacin (10(-6) M), and a nitric oxide synthesis inhibitor, N(omega)-nitro-L-arginine methylester (3 x 10(-5)). The same protocol was applied to both endothelia (+) and endothelia (-) aortic rings. The preparations precontracted with prostaglandin F2alpha (10(-7) mol l(-1)) were stimulated with electrical field stimulation at a frequency of 10 Hz as square-wave pulses of 50 V (0.2 ms) in the presence of a noradrenaline reuptake inhibitor desipramine (10(-7) mol l(-1)) and a nonselective beta-blocker propranolol (10(-6) mol l(-1)). Drugs were added at ineffective concentration of 10(-7) mol l(-1). Tetrodotoxin (10(-7) mol l(-1)) was added to test whether the changes were dependent on the neuronal response. RESULTS:Pancuronium and rocuronium relaxed aortic rings precontracted by prostaglandin F2alpha in a dose-dependent manner, but vecuronium and mivacurium did not. The relaxation effect of pancuronium and rocuronium was endothelium independent because there was not a significant response difference from the endothelium-denuded group. CONCLUSION: In conclusion, their relaxation effect may be due to an increase in prostaglandin synthesis. The increased relaxation effect of these agents at electrical field stimulation may be by the decreasing effect of noradrenaline reuptake from nerve endings because a noradrenaline reuptake inhibitor desipramine did not change this effect. Also, these neuromuscular agents may affect beta-receptors, because a nonselective beta-blocker agent, propranolol, decreased their electrical field stimulation-induced relaxations.