The effects of propofol, a novel intravenous anesthetic agent, an regulation of vascular tone in isclateo rabbit pulmonary arteries

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By measuring isometric contractions, intracellular concentration of CaィイD12+ィエD1([CaィイD12+ィエD1]ィイD2iィエD2) and membrane potential changes, we found that propofol had many actions on agonist-induced CaィイD12+ィエD1-mobilization mechanisms in smooth muscle cells of rabbit mesenteric arteries : (1) inhibition of CaィイD12+ィエD1 influxes through L-type CaィイD12+ィエD1 channels, (2) inhibition of agonist-induced CaィイD12+ィエD1 release from intracellular CaィイD12+ィエD1 storage sites, (3)inhibition of [CaィイD12+ィエD1]ィイD2iィエD2 removal mechanisms. In addition, propofol inhibits the synthesis of prostacyclin, but not of EDHF, in endothelial cells of these arteries. Propofol is known to be a scavenger against reactive oxygen species (ROS). However, the physiological function of these ROS has not been clarified in resistance vessels. Therefore, the effect of HィイD22ィエD2OィイD22ィエD2, one of major ROS in vascular tissues, was first examined on regulation of vascular tones in rabbit mesenteric arteries. As a result, we found that (1) HィイD22ィエD2OィイD22ィエD2 attenuated the contraction induced by norepinephrine in endothelium-intact and -denuded preparations, (2) HィイD22ィエD2OィイD22ィエD2 increases the synthesis of prostanoids (PGEィイD22ィエD2, PGIィイD22ィエD2) in both preparations, (3) HィイD22ィエD2OィイD22ィエD2 hyperpolarizes a smooth muscle cell membrane through an activation of glibenclamide-sensitive KィイD2ATPィエD2 channels. Now, we are trying to examine the action of propofol on these HィイD22ィエD2OィイD22ィエD2-induced responses in rabbit mesenteric arteries. In a future, using rabbit intrapulmonary arteries, we are planning to clarify the physiological and pathophysiological roles of HィイD22ィエD2OィイD22ィエD2 and also to examine the action of propofol on the HィイD22ィエD2OィイD22ィエD2-induced responses.