BACKGROUND: The minimal effect of etomidate on cardiovascular function sets it apart from other rapid fast-acting induction agents. Clinically, etomidate has been reported to cause minimal effects on systemic hemodynamics and PVR. There are few reports of direct effects of etomidate in pulmonary vessels or other vascular beds. METHODS: We studied the effects of etomidate on the tension of the aortic smooth muscle using an isolated rat thoracic aortic preparation. We studied the cumulative effect of etomidate in a rat thoracic aorta after phenylephrine (PE) pretreating, the cumulative effect of phenylephrine (PE) in a rat thoracic aorta with or without endothelium after etomidate pretreating, the effect of L-NAME and indomethacin and metylene blue in a rat thoracic aorta contractile response for phenylephrine after etomidate pretreating, and the effects of etomidate on a phenylephrine and ECF Ca2 induced contraction in a rat thoracic aorta. RESULTS: Etomidate produced dose-dependent relaxation and these relaxation responses were significantly less in a thoracic aorta with denuded endothelium than in a thoracic aorta with intact endothelium. Response of PE contraction with etomidate was increased by pretreatment with L-NAME and methylene blue, but was decreased by pretreatment with indomethacin in intact endothelium. Response of PE contraction had no significant change in Ca2 free, but Etomidate significantly attenuated the response of PE contraction to Ca2 entry. CONCLUSIONS: We have found that vasodilation produced by etomidate is endothelium-dependent and this effect is related with cyclooxygenase inhibition and also guanylate cyclase activation. In addition, a relaxation effect is caused by an extracellular Ca2 influx blockade through receptor-operated calcium channels.