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Weightlessness or simulated weightlessness would induce functional adaptation of arteries eliciting postflight orthostatic intolerance,but the change of angiotensin Ⅱ(Ang Ⅱ)elicited vasoconstriction has never been reported.Caveolae are invaginations on cell membrane enriched of cholesterol and sphingolipids crucial for the contraction of vascular smooth muscle cells(VSMCs).We tried to postulate how the vasoconstriction to Ang Ⅱ was adapted by simulated weightlessness,the role of caveolae in the adaptation and whether cholesterol could regulates the effect.4 wk hindlimb-unweighted(HU)rat was used to simulate the effect of weightlessness.Abdominal aorta(AA),thoracic aorta(TA)and carotid artery(CA)were isolated from control(CON)or HU rats,and then the vasoconstriction to Ang Ⅱ was measured by isometric force recording.Morphology of caveolae was explored by the method of transmission electron microscope(TEM).The binding of angiotensin Ⅱ type 1 receptor(AT1)and caveolin-1(cav-1),the structural protein of caveolae,was detected through coimmunoprecipitation and Western blot.We first found maximal developing force(Emax)of the Ang Ⅱ elicited vasoconsitriction was decreased in AA,unchanged in TA and increased in CA after HU,while EC50 of the response was increased significantly in all the three arteries so did the extent of AT1 desensitization upon activation.Next,we found caveolae amount on VSMCs of AA,TA and CA was reduced by HU,while the protein content of cav-1 did not change.Ang Ⅱ promoted the binding of AT1 and cav-1 which could be prevented significantly by HU in all the three arteries.Both the caveolae amount and the binding of AT1 and cav-1 could be recovered by pretreatment of cholesterol(10 mM,1h).Correspondingly,EC50 of the response,as well as AT1 desensitization in the three arteries were also be reinstated on chol incubation.The result indicates modified caveolae on VSMCs interfere with the binding of AT1 and cav-1 facilitating functional adaptation of arteries to HU and it might be one of countermeasures for postflight orthostatic intolerance to increase the level of cholesterol.