Effects of dexmedetomidine in the mesenteric artery and the aorta of endotoxin induced rat

Abstract

pp. 51-77 of this journal issue contain abstracts of the 12th ICSM Annual Scientific Meeting 2008INTRODUCTION: Dexmedetomidine is an anesthetic agent, with known α2 adrenergic effects, used both in humans and in animals. The present experiments were designed to compare the vascular effects of dexmedetomidine in rat arteries during normal and septic conditions. METHODS: Ten weeks old male normal Sprague Dawley rats were used. The mesenteric arteries and thoracic aortae were dissected and suspended into 5 ml organ chambers for isometric tension recording. In some experiments, endotoxin from E-coli lipopolysaccharide (O55:B5) was injected 10 mg/kg intraperitoneally 2 or 24 hours before the start of experiments. RESULTS: In the mesenteric arteries, dexmedetomidine caused concentration-dependent relaxations (with a maximal response averaging 50%). It induced smaller relaxations in the rat aorta (maximal response averaging 10%). At concentrations above 100 nM, the relaxation was reverted to a concentration-dependent contraction in the mesenteric arteries. In the presence of L-NAME (a nitric oxide synthase inhibitor) and after the removal of the endothelium, the drug-induced relaxation was abolished in mesenteric arteries. The secondary contraction was reduced when prazosin (α1 adrenergic antagonist) was added to the bath solution. After endotoxin administration, the relaxations in mesenteric arteries were reduced to around 20% in both 2 and 24 hours treatment durations. Endotoxin did not affect the magnitude of the secondary contraction, which were still abolished in the presence of prazosin. CONCLUSIONS: The vascular effects of dexmedetomidine depend on the vascular bed studied. The vasodilatation caused by dexmedetomidine is nitric oxide and endothelium-dependent in the rat mesenteric artery. This relaxation can be reduced during sepsis, while α1 adrenoceptors are responsible for the secondary contraction at higher concentrations of dexmedetomidine.link_to_OA_fulltex